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PubMed2001

DDT resistance in Drosophila correlates with Cyp6g1 over-expression and confers cross-resistance to the neonicotinoid imidacloprid.

Mutagenesis can be used as a means of predicting likely mechanisms of resistance to novel classes of insecticides. We used chemical mutagenesis in Drosophila to screen for mutants that had become resistant to imidacloprid, a neonicotinoid insecticide. Here we report the isolation of two new dominant imidacloprid-resistant mutants. By recombinational mapping we show that these map to the same location as Rst(2)DDT. Furthermore, we show that pre-existing Rst(2)DDT alleles in turn confer cross-resistance to imidacloprid. In order to localize the Rst(2)DDT gene more precisely, we mapped resistance to both DDT and imidacloprid with respect to P-element markers whose genomic location is known. By screening for recombinants between these P-elements and resistance we localized the gene between 48D5-6 and 48F3-6 on the polytene chromosome map. The genomic sequence in this interval shows a cluster of cytochrome P450 genes, one of which, Cyp6g1, is over-expressed in all resistant strains examined. We are now testing the hypothesis that resistance to both compounds is associated with over-expression of this P450 gene.

Animals↗
PubMed2001

Diversity among clinical isolates of penicillin-resistant Streptococcus mitis: indication for a PBP1-dependent way to reach high levels of penicillin resistance.

A total of 12 non-epidemiologically related clinical isolates of Streptococcus mitis that showed different levels of resistance to penicillin were studied. Membrane-protein profiles and penicillin-binding protein (PBP) patterns showed a great polymorphism; and patterns of 4-7 PBPs, with sizes that ranged from approximately 101 kDa to approximately 40 kDa, were detected in each strain. No association could be found between PBP pattern and resistance level to penicillin among these isolates. Arbitrarily primed PCR confirmed the genetic diversity among this group of streptococci. One of the isolates of intermediate level of resistance to penicillin, which showed a PBP pattern similar to that of the high-resistance strains, was used as a laboratory model to analyse the mechanism underlying high-resistance acquisition by these strains. A 14-fold increase in penicillin resistance was obtained after a single selection step, which resulted in a decrease in penicillin affinity for PBP1. The size of this PBP (92 kDa) and the differences in PBP profiles of the penicillin-resistant clinical isolates suggest the existence in S. mitis of PBP-mediated mechanisms to acquire high-level resistance to penicillin, among which alterations in PBP1 seem to play a main role, in contrast to the PBP2X mediated mechanism described for other streptococci.

Bacterial Proteins↗
PubMed1989

Atypical multidrug resistance in CCRF-CEM cells selected for high level methotrexate resistance: reactivity to monoclonal antibody C219 in the absence of P-glycoprotein expression.

A series of CCRF-CEM sublines selected for extreme resistance to methotrexate has been shown previously to exhibit cross resistance to a number of agents belonging to the multidrug resistance phenotype (J.Natl.Cancer Inst.1989; 81, 1250-1254). The role of the mdr1 gene and its product (P-glycoprotein) in this atypical pattern of multidrug resistance has now been investigated. Southern and Northern analyses failed to demonstrate any amplification, rearrangement or over-expression of the mdr1 gene in the drug-resistant cells. Similarly, monoclonal antibodies MRK16 and JSB1 revealed no increase in the amount of P-glycoprotein present. By contrast, monoclonal antibody C219 detected a 170 kDa protein in all sublines, and in highest concentration in the most resistant cells. The results raise the possibility that a novel, C219-reactive protein may mediate resistance to both methotrexate and members of the multidrug resistance family.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

A human small cell lung carcinoma cell line, resistant to 4'-(9-acridinylamino)-methanesulfon-m-anisidide and cross-resistant to camptothecin with a high level of topoisomerase I.

N417/AMSA cells, about 80-fold resistant to mAMSA [4'-(9-acridinylamino)-methanesulfon-m-anisidide], were obtained by serial passages of the parental human small cell lung carcinoma NCI-N417 (N417/p) in stepwise drug concentrations. The N417/AMSA cells were found to be 114-, 100-, and 9-fold cross-resistant to the topoisomerase II (Topo II) inhibitors VM26, VP16 and Doxorubicin (DXR); they showed a 2-fold decrease in Topo II activity. Interestingly, N417/AMSA cells which exhibited a 3-fold increase in topoisomerase I (Topo I) activity were 28-fold cross-resistant to camptothecin (CPT), a specific inhibitor of Topo I. In order to investigate the cellular mechanisms leading to the development of resistance, the effects of mAMSA and CPT on parental and resistant cell lines were analysed by alkaline elution. A decrease in DNA single-strand breaks (DNA-SSB) was observed in N417/AMSA cells treated with mAMSA or CPT compared to parental cells. Similar differences were obtained in isolated nuclei, suggesting that no modification of mAMSA and CPT accumulation occurred in resistant cells. Topo I was purified from N417/p (Topo I/p) and N417/AMSA (Topo I/AMSA) cells in the exponential phase of growth, and the inhibitory effects of CPT on relaxation activities were determined. Topo I/AMSA was found to be about 7-fold less sensitive to CPT than Topo I/p, suggesting the possible involvement of a mutation outside the gene region sequenced (codons 420 to 642) or post-translational modifications of the Topo I enzyme. These data indicate that increased Topo I activity cannot be related to CPT resistance, and suggest that mAMSA can generate multiple cellular modifications which may be involved in resistance to various drugs.

Amsacrine↗
PubMed1994

Cross-resistance to heavy metals in hydrogen peroxide-resistant CHO cell variants.

Hydrogen peroxide-resistant Chinese hamster ovary (CHO) cells displayed cross-resistance to CdCl2, HgCl2 and NaAsO2 but not to Na2Cr2O7, ZnCl2, NiCl2 and CuSO4. Resistance to hydrogen peroxide and to the metals was partially retained by these cells for many generations despite growth in drug-free medium. The loss of resistance was a slow process, and was different for the various metal compounds. Cell variants had a slightly higher content of non-protein intracellular thiols (NPSH) than sensitive cells. This biochemical feature did not seem to be the cause of resistance to CdCl2 but accounted for at least part of the resistance to HgCl2 and NaAsO2. Increased metallothionein synthesis did not seem to be responsible for the metal-resistant phenotype. These results suggest that resistance to specific metal compounds in cultured mammalian cells adapted to hydrogen peroxide is dependent on a number of factors which differ for the various metal compounds and which are characterized by a different stability.

Animals↗
PubMed1995

Vascular resistance quantification in high flow resistance areas using the Doppler method.

The objective of the present study is to define and validate on an animal model (ewe) a new Doppler parameter for the assessment and monitoring of the vascular resistances in high resistance to flow areas (lower limbs, placenta with vascular disease). The high resistance index (HRI) was derived from the transmission line theory and defined as: HRI = D/S with S the amplitude of the systolic peak and D that of the diastolic reverse flow. Validation of the HRI was performed on adult ewes. Distal lower limb vascular resistances were evaluated from the Doppler femoral waveform (HRI) and compared with the classic vascular resistances (Rv), calculated from pressure and flow (mmHg/mL/min). The femoral flow variations were measured by duplex (echo-Doppler) method and the mean pressure through an arterial catheter inserted into the abdominal aorta. Two tests were used in this study: (1) A calibrated venous compression of the lower limbs extremity: The femoral flow dropped by 29%, the pressure and heart rate did not change, the HRI increased by 37% (p < 0.01), and the vascular resistance (Rv) by 46% (p < 0.01). (2) The intravenous injection of 1 mg adrenaline: The arterial pressure increased by 70% (p < 0.001), the heart rate and femoral flow dropped by 50% (p < 0.001), and 35% (p < 0.001), the HRI increased by 70% (p < 0.01) and the vascular resistances (Rv) by 140% (p < 0.01). During the two tests, the HRI changed in proportion with the "classic" vascular resistances.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Reversal of doxorubicin-resistance in sarcoma 180 tumor cells by inhibition of different resistance mechanisms.

Resistance of tumor cells to doxorubicin is a multifactorial phenomenon. In the present investigation, the ability of resistance modifiers against different resistance mechanisms was analysed. Substances which block P-glycoprotein (P-170) function circumvented resistance of doxorubicin-resistant sarcoma 180 (S180) cells completely (verapamil, thioridazine) or partially (hycanthone), whereas inhibitors of glutathione S-transferase (ethacrynic acid, N-ethylmaleimide, buthionine sulfoximine), and protein kinase C (staurosporine, acridine orange) caused only a partial reversion of resistance. In contrast, an inhibitor of alkaline phosphatase (levamisole) did not overcome doxorubicin-resistance. These results indicate that P-glycoprotein blockers might be more effective to modulate doxorubicin-resistance of S180 cells as compared to other modifiers. Further investigations using other MDR cell lines are required to clarify the generality of these findings.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Evaluation of the CombiChip Mycobacteria Drug-Resistance detection DNA chip for identifying mutations associated with resistance to isoniazid and rifampin in Mycobacterium tuberculosis.

The CombiChip Mycobacteriatrade mark Drug-Resistance Detection DNA chip, recently developed by GeneIn (Pusan, South Korea), is an oligonucleotide microchip coupled with polymerase chain reaction for the detection of mutations associated with resistance to isoniazid (INH) and rifampin (RIF). This oligonucleotide chip was compared with DNA sequencing and phenotypic drug susceptibility testing with 69 INH- and/or RIF-resistant and 27 all tested drug-susceptible Mycobacterium tuberculosis isolates. Two selected codons (the katG codon 315 and inhA15) allowed identification of 84.1% of INH-resistant isolates and 100% of RIF resistance were detected by screening for 7 codons: rpoB511, rpoB513, rpoB516, rpoB522, rpoB526, rpoB531, and rpoB533. The overall specificity of this oligonucleotide chip for detecting INH and RIF resistance were 100 and 95.3%, respectively. This level of sensitivity and specificity is concordant with that from the determination of M. tuberculosis drug resistance by DNA sequencing. This oligonucleotide chip is a rapid and reliable genotypic method capable of detecting multiple mutations associated with INH and RIF resistance simultaneously in a single microchip slide.

Antitubercular Agents↗
PubMed2005

Drug resistance in ovarian cancer: the emerging importance of gene transcription and spatio-temporal regulation of resistance.

Resistance to carboplatin plus paclitaxel, one of the most active drug combinations in ovarian cancer, is the major barrier to the successful long-term treatment of this disease. Understanding the mechanisms involved is a first step towards rational strategies to overcome drug resistance and is an area of intense research effort. Recent work has identified several gene families which appear to contribute to the evolution of drug resistance and which are involved in regulating DNA damage, apoptosis and survival signalling. These genes may be co-ordinately regulated as part of a gene expression program that confers drug resistance through multiple pathways. The subcellular localisation of the gene products and their kinetic regulation following exposure to chemotherapeutic agents may also play a part in the development of drug resistance. This provides a more complex paradigm for drug resistance in which the steady-state expression of a single gene may not be predictive of response to therapy. Nevertheless, the identification of critical genes, most relevant to the development of clinical drug resistance, is now feasible through microarray analysis of tumour samples, and strategies aimed at the circumvention of resistance can be developed using these data.

Animals↗
PubMed2004

The status of antimicrobial resistance in Taiwan among Gram-positive pathogens: the Taiwan Surveillance of Antimicrobial Resistance (TSAR) programme, 2000.

In the Taiwan Surveillance of Antimicrobial Resistance programme, isolates were collected from 21 hospitals over a 3-month period in 2000 (TSAR II) and rates of resistance in Gram-positive pathogens were determined. Resistance rates were high including oxacillin resistance in Staphylococcus aureus (60%) and coagulase-negative staphylococci (80%), high-level gentamicin resistance (HLGR) in Enterococcus faecalis (60%) and penicillin non-susceptibility in Streptococcus pneumoniae (69%). Oxacillin resistance had increased from 1998 (TSAR I) and may be spreading into outpatient settings. In contrast, less than 2% enterococci were vancomycin-resistant. No linezolid resistance was found in either staphylococci or enterococci.

Anti-Bacterial Agents↗
PubMed2004

Antimicrobial resistance of Neisseria gonorrhoeae in Japan, 1993-2002: continuous increasing of ciprofloxacin-resistant isolates.

Susceptibility testing was conducted on 1357 isolates of Neisseria gonorrhoeae isolated from 1993 through 2002 in Japan to assess the antimicrobial resistance. Selected isolates were characterised by auxotype and analysis was done for mutations within the quinolone resistance-determining region (QRDR) in the gyrA and parC genes, which confer fluoroquinolone resistance to the organism. Isolates with ciprofloxacin resistance increased significantly from 6.6% (1993-1994) to 73.5% (2002). The proportion of plasmid-mediated penicillin-resistant isolates (PPNG) decreased significantly from 7.9% (1993-1994) to 0.9% (2002). The percentage of chromosomal-mediated resistance to penicillin decreased from 27.4% in 2000 to 12.0% in 2001 but increased to 28.9% in 2002. The proportion of isolates with any type of resistance to tetracycline decreased from 24.7% in 2000 to 13.9% in 2001 and then increased to 22.3% in 2002. The proportion of prototrophic isolates significantly decreased from 84.4% in 1992-1993 to 7.7% in 2001, while that of the proline-requiring isolates significantly increased from 4.4% in 1992-1993 and 80.8% in 1998. The proline-requiring isolates were less susceptible to ciprofloxacin than the prototrophic or arginine-requiring isolates. Of 87 isolates resistant to ciprofloxacin, 2 (2.3%) contained five amino acid substitutions within the GyrA and ParC proteins, 76 (87.4%) contained three or four amino acid substitutions and 9 (10.3%) contained one or two amino acid substitutions.

Amino Acid Substitution↗
PubMed2005

Analysis of mutations within multiple genes associated with resistance in a clinical isolate of Neisseria gonorrhoeae with reduced ceftriaxone susceptibility that shows a multidrug-resistant phenotype.

A Neisseria gonorrhoeae strain with a reduced susceptibility to ceftriaxone (minimum inhibitory concentration (MIC) = 0.5 microg/mL) was isolated among 398 clinical isolates obtained from 2000-2001 in Fukuoka City, Japan. The N. gonorrhoeae strain was negative for penicillinase production but it showed multidrug resistance against penicillin (MIC = 8 microg/mL), tetracycline (MIC = 4 microg/mL), azithromycin (MIC = 0.5 microg/mL) and ciprofloxacin (MIC = 16 microg/mL). The molecular mechanisms of the multidrug-resistant phenotype in this strain were analysed. Polymerase chain reaction and direct DNA sequencing were performed to identify mutations within the penA, ponA, mtrR, penB, gyrA and parC genes of the gonococcal strain, which thus explain the multidrug-resistant phenotype. The N. gonorrhoeae strain contained a significantly different sequence of the penA gene from that of the ceftriaxone-susceptible strains. Some regions of the transpeptidase domain within this penA gene were closely similar to those found in other Neisseria species such as Neisseria subflava, Neisseria flavescens or Neisseria perflava/sicca. This strain also included a ponA mutation that is associated with high-level resistance to penicillin, mtrR mutations that mediate overexpression of the MtrCDE efflux pump responsible for resistance to hydrophobic agents such as azithromycin, and penB mutations that reduce porin permeability to hydrophilic agents such as tetracycline. Moreover, this strain contained gyrA and parC mutations that confer high-level resistance to ciprofloxacin. These results indicate the emergence of a N. gonorrhoeae strain with reduced susceptibility to ceftriaxone, which also showed a multidrug-resistant phenotype that can be explained by the presence of multiple loci mutations associated with antibiotic resistance.

Amino Acid Sequence↗
PubMed2006

Mutational patterns associated with the 69 insertion complex in multi-drug-resistant HIV-1 reverse transcriptase that confer increased excision activity and high-level resistance to zidovudine.

Human immunodeficiency virus type 1 (HIV-1) strains having dipeptide insertions in the fingers subdomain and other drug resistance-related mutations scattered throughout their reverse transcriptase (RT)-coding region show high-level resistance to zidovudine (AZT) and other nucleoside analogues. Those phenotypic effects have been correlated with their increased ATP-dependent phosphorolytic activity on chain-terminated primers. Mutations T69S and T215Y and a dipeptide insertion (i.e. Ser-Ser) between positions 69 and 70 are required to achieve low-level resistance to thymidine analogues. However, additional amino acid substitutions are necessary to achieve the high-level phenotypic resistance to AZT shown by clinical HIV isolates carrying a dipeptide insertion in their RT-coding region. In order to identify those mutations that contribute to resistance in the sequence context of an insertion-containing RT derived from an HIV clinical isolate (designated as SS RT), we expressed and purified a series of chimeric enzymes containing portions of the wild-type or SS RT sequences. ATP-mediated excision activity measurements using AZT- and stavudine (d4T)-terminated primers and phenotypic assays showed that molecular determinants of high-level resistance to AZT were located in the fingers subdomain of the polymerase. Further studies, using recombinant RTs obtained by site-directed mutagenesis, revealed that M41L, A62V and in a lesser extent K70R, were the key mutations that together with T69S, T215Y and the dipeptide insertion conferred high levels of ATP-dependent phosphorolytic activity on AZT and d4T-terminated primers. Excision activity correlated well with AZT susceptibility measurements, and was consistent with phenotypic resistance to d4T. Structural analysis of the location of the implicated amino acid substitutions revealed a coordinated effect of M41L and A62V on the positioning of the beta3-beta4 hairpin loop, which plays a key role in the resistance mechanism.

Adenosine Triphosphate↗
PubMed2006

The role of Leishmania enriettii multidrug resistance protein 1 (LeMDR1) in mediating drug resistance is iron-dependent.

In parasitic protozoan Leishmania enriettii, the role of a multidrug resistance (mdr) gene LeMDR1 (L. enriettii multidrug resistance 1) in mediating vinblastine resistance has been previously demonstrated by association, transfection and "gene knockout" studies. LeMDR1 has been shown to be located intracellularly and it was proposed to mediate drug resistance by sequestering drugs into intracellular organelles rather than by active efflux. Here we compared LeMDR1 overexpressed cell lines (Vint3 and V160), wild type (Le) and LeMDR1 "double knockout" mutant (LeMDR1-/-) and demonstrated that LeMDR1 gene copy number was associated with (1) higher level of intracellular iron, (2) increased sensitivity to an iron-dependent antibiotic, streptonigrin and (3) increased enzyme activity of an iron-sulfur-containing mitochondrial enzyme, aconitase. This result suggests that the normal function of LeMDR1 is related to mitochondrial iron homeostasis. To test such hypothesis, we have used the LeMDR1-overexpressing mutant V160 and LeMDR1-/- mutant to determine how iron level can affect its resistance level to drugs targeting either cytosol (vinblastine) or mitochondria (rhodamine 123 and pentamidine). It was found that the resistance level of V160 to vinblastine can be increased by iron whereas resistance to both rhodamine 123 and pentamidine can be increased by iron depletion and vice versa. Iron treatment can potentiate rhodamine 123 and pentamidine accumulation whereas iron deprivation can cause the reduction of rhodamine 123 accumulation. Our result highly suggests that LeMDR1's function in mediating drug resistance is iron-dependent.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Relative replication fitness of efavirenz-resistant mutants of HIV-1: correlation with frequency during clinical therapy and evidence of compensation for the reduced fitness of K103N + L100I by the nucleoside resistance mutation L74V.

Efavirenz resistance during HIV-1 treatment failure is usually associated with the reverse transcriptase mutation K103N. L100I, V108I, or P225H can emerge after K103N and increase its level of efavirenz resistance. K103N + L100I is the most drug-resistant of the double mutants but is the least common clinically. We hypothesized that differences in replication efficiency, or fitness, influence the relative frequencies of these secondary efavirenz resistance mutations in clinical isolates. We measured fitness of each secondary mutant introduced into HIV(NL4-3), alone and in combination with K103N, using growth competition assays in H9 cells. In the absence of efavirenz, the fitness of V108I was indistinguishable from wild type. K103N, L100I, and P225H were minimally, but consistently, less fit than wild type. K103N + L100I had a greater reduction in fitness and was less fit than K103N + V108I and K103N + P225H. The fitness defect of K103N + L100I relative to K103N was completely compensated for by the addition of the nucleoside resistance mutation L74V. In the presence of efavirenz, L100I was less fit than K103N, and K103N + L100I was more fit than K103N + V108I. Our studies suggest the primary driving force behind the selection of secondary efavirenz resistance mutations is the acquisition of higher levels of drug resistance, but the specific secondary mutations to emerge are those with the least cost in terms of replication efficiency. In addition, nucleoside and NNRTI resistance mutations can interact to affect HIV replication efficiency; these interactions may influence which mutations emerge during treatment failure. These studies have important implications for the design of more durable NNRTI-nucleoside combination regimens.

Alkynes↗
PubMed2000

Increased mRNA levels of xeroderma pigmentosum complementation group B (XPB) and Cockayne's syndrome complementation group B (CSB) without increased mRNA levels of multidrug-resistance gene (MDR1) or metallothionein-II (MT-II) in platinum-resistant human ovarian cancer tissues.

Tumor tissue specimens from human ovarian cancer patients were assessed for relative mRNA abundance levels of several genes thought to be involved in the development of in vitro drug resistance in this disease. Higher mRNA levels of Xeroderma pigmentosum group B (XPB), which links DNA repair with DNA transcription, and of Cockayne's syndrome group B (CSB), which is essential for gene-specific repair, were observed in tumor tissues that were clinically resistant to platinum-based chemotherapy, as compared with tissues from patients responding to therapy. In a cohort of 27 patients, mRNA levels of XPB averaged 5-fold higher in platinum-resistant tumors (P = 0.001); and for CSB, mRNA levels averaged 6-fold higher but with greater variability (P = 0.033). Concurrently, these platinum-resistant tumor tissues did not exhibit significantly higher mRNA levels for the MDR1 (multidrug-resistance) gene (P = 0.134) or of the metallothionein-II (MT-II) gene (P = 0.598). Since these platinum-resistant tumors also show higher mRNA levels of ERCC1 and XPA, platinum resistance appears to be associated with concurrent up-regulation of four genes (XPA, ERCC1, XPB, and CSB). These four genes participate in DNA damage excision activity, gene-specific repair, and linkage of DNA repair with DNA transcription. These data suggest that concurrent up-regulation of genes involved in nucleotide excision repair may be important in clinical resistance to platinum-based chemotherapy in this disease.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

World-wide antibiotic resistance in methicillin-resistant Staphylococcus aureus.

Antibiotic resistance patterns were determined for 106 strains of methicillin-resistant Staphylococcus aureus (MRSA) from 21 countries. Resistance to gentamicin, tobramycin, netilmicin, amikacin, streptomycin, or erthromycin was recorded in more than 90% of strains. Resistance to the other compounds tested was as follows: tetracycline 86%, minocycline 76%, trimethoprim 69%, clindamycin 66%, neomycin 59%, chloramphenicol 39%, rifampicin 26%, fosfomycin 22%, ciprofloxacin 17%, fusidic acid 12%, bacitracin 2%, and novobiocin 1%. All the stains were sensitive to mupirocin, pristinamycin, ramoplanin, teicoplanin, and vancomycin. There were geographical patterns of resistance: MRSA from the UK and Australia were predominantly resistant to trimethoprim, whereas many strains from centres in Europe and the USA were sensitive. MRSA that were resistant to ciprofloxacin were of French and German origin. 15 strains, 12 of which came from France, Turkey, or Brazil, were resistant either to thirteen or to fourteen agents.

Administration, Topical↗
PubMedDate not supplied

In vitro establishment of cis-diammine-dichloroplatinum(II) resistant lung cancer cell line and modulation of apoptotic gene expression as a mechanism of resistant phenotype.

After exposure of H460 cells to an increasing concentrations of cis-diammine-dichloroplatinum(II) (cisplatin, CDDP) for 6 months, cisplatin resistant cells were isolated (H460/CIS). The biologic behaviors of H460 and H460/CIS cells were tested using animal experiments. Only the resistant cells developed lung metastases despite cisplatin treatment. The characteristics of H460/CIS cells are as follows, MTT analyses revealed that H460/CIS cells were markedly resistant to cisplatin compared with their parental cells. Also, H460/CIS cells exhibited cross-resistance to DNA damaging agents such as doxorubicin (DXR) and etoposide. Cisplatin treatment dramatically increased p53 expression in parental cells but not in H460/CIS cells which expressed basal levels of p53. Without cisplatin treatment, Bcl-2 and Bax were expressed in H460/CIS cells, but not in parental cell. Our data suggested that p53, Bax and Bcl-2 were up-regulated in H460/CIS cells. These changes could explain some of the mechanisms of cisplatin resistance. Thus, H460/CIS could be useful to investigate the mechanisms of drug resistance to cisplatin including apoptotic gene expressions conferring drug resistance, thereby making progress in the treatment of cisplatin-resistant tumor cells.

Animals↗