Biomedical subjects
Publications and source records attributed to Ding Ma.
Submicrometer-sized mesoporous silica SBA-15 with cuboidlike morphology has been prepared by using excess amounts of decane as cosolvent in the presence of NH4F. The channels of the resulting material run parallel to the short axis of the cuboid-like SBA-15. It has also been found that the materials have a well-ordered channel structure with pore size ca. 12 nm.
Transforming growth factor-beta (TGF-beta) may cause cell cycle arrest, terminal differentiation, or apoptosis in most normal epithelial cells, whereas most malignant cell lines are resistant to TGF-beta. Mechanisms of resistance to TGF-beta caused by modulation of cell cycle regulators and/or inactivation of components of the TGF-beta signaling transduction pathway such as C-myc and Smad4 are not well understood. To investigate the potential association between loss of sensitivity to TGF-beta and expression status of transforming growth factor receptor II (TbetaR II) , Smad4, CDC25A and C-myc in 14 cell lines derived from ovarian cancer, the expression levels of these genes were detected by semi-quantitative RT-PCR. Normal ovarian surface tissues were used as controls. The expression of TbetaR II was detectable in all of 14 cell lines. The expression of Smad4 was decreased in 10 cell lines and 9 cell lines overexpressed CDC25A, as compared to normal controls. CDC25A gene was overexpressed with 88% (8/9) in tumorigenic cell lines as determined by xenografts in nude mice, and only in 20% (1/5) of non-tumorigenic cell lines (P<0.05). C-myc was not overexpressed in any of these cell lines. The loss of sensitivity to TGF-beta of cell lines derived from ovarian cancers may be related to a decreased expression of Smad4, which mediates TGF-beta induced growth inhibition, and/or an overexpression of CDC25A. This overexpression of CDC25A correlates with increased tumorigenicity of ovarian cancer cell lines. The loss of sensitivity to TGF-beta is not associated with a lack of TbetaR II.
The relationship of connexin43 (Cx43) and bystander effect in ovarian tumor cells in herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) gene therapy in vitro was explored and the effect of all-trans retinoic acid (RA) on the expression of Cx43 and bystander effect investigated. The Cx43 expression was detected by flowcytometry, Western blot, and immunofluorescence in two ovarian tumor cell lines OVCAR3, CaOV3 before and after RA treatment. Bystander effect was determined by the cells growth inhibitory rate with methyl thiazolyl tetrazolium. Following exposure to ganciclovir, there was much greater bystander killing in OVCAR3 than that in CaOV3 (P<0.05). The expression of Cx43 was detected in OVCAR3 by flowcytometry and Western blot, but it could not be detected in CaOV3. The expression of Cx43 in both cell lines could be induced by RA. Immunofluoresence staining showed that Cx43 protein of OVCAR3 was located on membrane surface, whereas CaOV3 in cytoplasm. RA could not change the location of Cx43 protein in both cell lines. There is relationship between Cx43 expression and HSV-TK/GCV bystander effect. HSV-TK/GCV bystander effect can be enhanced by RA in ovarian cancer.
To construct eukaryotic expression vector expressing full length anti-sense pituitary tumor transforming gene (PTTG) mRNA and observe its blocking effect on the potential invasion of human ovarian carcinoma cell line SK-OV-3. PCR primers containing designed enzyme cut sites were used for cloning full-length PTTG gene fragment, and the resulting PCR product was inserted into the eukaryotic vector pcDNA3.1 in the antisense direction. The recombinant vector was then transfected into SK-OV-3 by Lipofectamine. The positive cell clone was screened by G418, PTTG and bFGF at protein level expression were detected by Western blot. The biological behavior change of transfection positive cells was observed by colony formation in soft agar assay. Our results showed that SK-OV-3 clones stably expressing full-length recombinant pcDNA3.1-PTTGas were obtained. The expressions of PTTG and bFGF protein in transfected cells were decreased by 61.5% and 52.3%, respectively as compared with non-transfected ones. The number of colony formation was reduced significantly in transfected cells as compared with empty vector transfected and non-transfected cells. It is concluded that the recombinant vector pcDNA3.1-PTTGas is a novel tool and provides an alternative anti-sense gene therapy targeted at PTTG in human carcinoma.
GOALS: Resistance to cisplatin is the main reason for treatment failure in ovarian cancer. Apoptosis is the main mechanism of action of most cancer chemotherapeutic agents. The apoptosis-associated proteins expressed in cisplatin-sensitive (A2780, COC1) and -resistant (A2780/DDP, COC1/DDP) ovarian cancer cell lines, as well as their effects on caspase-3 activity in these cells, were studied by reverse transcriptase polymerase chain reaction and Western blot analysis. METHODS: The apoptotic ratios of A2780, COC1, A2780/DDP, and COC1/DDP cells after treatment with cisplatin were measured by flow cytometry. RESULTS: Expression of Bcl-2 and Bcl-X(L) in A2780/DDP and COC1/DDP cells was significantly higher than that in A2780 and COC1 cells, respectively. Expression of Bax and Bcl-Xs did not differ in cisplatin-resistant and -sensitive cells. Caspase-3 activity was reduced markedly and apoptotic ratios were significantly lower in A2780/DDP and COC1/DDP cells than in A2780 and COC1 cells after treatment with cisplatin. CONCLUSION: We conclude that overexpression of antiapoptotic proteins Bcl-2 and Bcl-X(L) and down-regulation of caspase-3 activity may be associated with cisplatin resistance in human ovarian cancer.
BACKGROUND & OBJECTIVE: Recent research had shown that survivin, a new member of the inhibitors of apoptosis proteins (IAP) family, which also plays an important role in mitosis and cell apoptosis, and selectively overexpressed in common human cancers. This study was designed to examine the expression of survivin and its correlation with expression of Fas and FasL in ovarian epithelial carcinoma. METHODS: Immunohistochemical assay (SP method) was used to detect the expression of survivin, Fas and FasL genes in 84 ovarian cancer tissues, 39 benign tumors of ovary, and 20 normal ovary tissues. RESULTS: The level of expression of survivin was higher in the patients with ovarian cancer (63.1%) than that in the patients with benign tumor of ovary (30.8%) and normal ovary tissues (0.0%)(P< 0.01). The expression level of survivin was strongly correlated with clinical stage and poor differentiation. The expression of Fas in ovarian cancer (23.8%) was significantly lower than that of ovarian benign tumor (53.8%) (P< 0.01). The expression rate of FasL was significantly higher in ovarian cancer (44.0%) than that in ovarian benign tumor (23.1%)(P< 0.05). Positive survivin expression was strongly correlated with Fas and FasL expression. CONCLUSION: (1) High expression of survivin may plays an important role in the development of ovarian cancer and could be a useful prognostic maker for patients with ovarian cancer.(2) The abnormal expression of Fas and FasL in ovary cancer and their correlation with survivin suggested that survivin might be in cooperation with Fas and FasL,which involved in the pathogenesis of ovarian cancer.
OBJECTIVE: Adenovirus vector-mediated herpes simplex virus thymidine kinase gene (ADV-TK) transfer in combination with ganiciclovir (GCV) is one of the major gene therapy strategies to eradicate tumor cells. This study was aimed at determining the in vivo anti-tumor efficacy of ADV-TK in combination with ganiciclovir (GCV). METHODS: A murine xenotransplant model of human small-cell lung cancer was established. ADV-TK was administrated by intra-tumoral injection followed by intraperitoneal administration of GCV. The anti-tumor efficacy was evaluated using index of tumor volume, relative tumor volume, tumor weight, relative tumor proliferative rate, and tumor growth curve. RESULTS: In the presence of GCV, ADV-TK effectively inhibited growth of human small-cell lung cancer in a dose-dependent fashion. An inhibition plateau was not observed within the current dosage range. ADV-TK at a dose of 6.0 x 10(9) viral particles/kg in the presence of GCV lead to 64.6% and 81.7% inhibition of tumor growth respectively in two independent experiments. ADV-TK or GCV alone caused slight inhibition of tumor growth, which was not statistically significant as compared to the negative control group (P > 0.05). CONCLUSION: ADV-TK followed by GCV is highly efficacious to inhibit the growth of human small-cell lung cancer in a murine xenotransplant model. The results presented here are encouraging to warrant a further clinical evaluation of the potential therapeutic benefits of this strategy.
BACKGROUND & OBJECTIVE: Metastasis is the leading cause of treatment failure and death of ovarian cancer. However, The molecular mechanisms associated with acquisition of metastatic ability in ovarian cancer are poorly understood. This study aimed at selecting the ovarian carcinoma cell lines with high frequency metastasis and studing the association between nm23-H1 gene expression in the model of ovarian carcinoma cells so as to provide the evidence for systematical experimental studying and clinical practice. METHODS: Each ovarian cancer cell line was transplanted subcutaneously into the flank of nude mice, and the metastatic behavior was evaluated by counting the number of lung tumor foci at different time. The metastatic tumors were cultured in vitro, then established substrain and transplanted subcutaneously three times. The mRNA and protein level of nm23 in 8 human ovarian cancer cell lines were examined. RESULTS: Four cell lines have high frequency metastatic potentiality. The subpopulation of cells with high frequency metastasis could be screened by injection several times. The expression of nm23 mRNA and protein in human ovarian cancer cells is inversely related to metastatic behavior in experimental animals (r=0.96, P=0.0001). CONCLUSION: The difference of metastatic potential, which was determined by genetic and molecular levels, was significant among different type of cell lines and subtypes. The expression of nm23 mRNA and protein in human ovarian carcinomas were correlated closely with the reduced metastatic behavior in experimental animals and may serve as a sensitive prognostic indicator of ovarian cancer.
OBJECTIVE: To study the mechanism of topotecan (TPT) resistance in ovarian cancer cell line. METHODS: A TPT-resistant ovarian cancer cell line A2780/TPT established in this laboratory was used in this study. Intracellular rhodamine fluorescence intensity of the TPT-resistant cells and parental cells were measured by flow cytometry. The gene expression of membrane protein transporter such as transporter P-glycoprotein (P-gp), multidrug resistance associated protein (MRP), breast cancer resistance protein (BCRP) was evaluated by RT-PCR. The antisense-phosphorothioate oligonucleotide (ASODN) including a translation initiation site of BCRP mRNA was transferred into resistant cells by liposome. RESULTS: Intracellular rhodamine fluorescence intensity of the resistant cells was 31.19% of that in the parental cells (P < 0.01). No expression of P-gp was demonstrated, and that of MRP was very weak in the TPT-resistant cells (relative expression value = 0.057). BCRP was overexpressed in the TPT-resistant cells (relative expression = 0.66), but not in the parental cells. Transfer of ASODN into resistant cells resulted in a 59.42% reduction of BCRP gene expression (P < 0.05) and an obviously increased intracellular rhodamine fluorescence intensity from 5.42 to 16.63 (P < 0.05). CONCLUSION: The overexpression of BCRP which mediated drug efflux may play an important role in the induction of TPT-resistance in ovarian cancer.
OBJECTIVE: To investigate the expression of RhoA, RhoC and their effector ROCK-1 in four ovarian cancer cell lines in vitro and their correlation with invasiveness. METHODS: Expression of RhoA, RhoC and ROCK-1 mRNA and protein in four ovarian cancer cell lines SW626, Skov-3, A2780 and Caov-3 was detected by RT-PCR and Western blot assay. Invasion assay was done in Boyden chamber. RESULTS: The expression levels of RhoA, RhoC and ROCK-1 mRNA and protein varied in the four different cell lines examined. The expression level of RhoC, but not RhoA and ROCK-1, was significantly correlated with the invasive capability of these cells in vitro (r = 0.95, P < 0.01). Expression of RhoA at the level of transcription was not correlated with that at the translation level. The expression of RhoA and RhoC did not correlate with that of ROCK-1. CONCLUSION: Expression level of RhoC may serve as an independent parameter in evaluating metastasis and become a new target in inhibiting ovarian cancer metastasis.
BACKGROUND & OBJECTIVE: Membrane-type 1 matrix metalloproteinase (MT1-MMP/MMP-14) is a newly discovered enzyme, which plays a key role in tumor metastasis. This study was to observe inhibitory effect of MT1-MMP antisense nucleotide on proliferation and invasive potential of human highly metastatic ovarian carcinoma cell line SW626. METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to amplify MT1-MMP cDNA fragments with 2 different restriction sites at its 5c-end. RT-PCR products were cloned into plasmid pcDNA3.1 in antisense direction. The recombinant pMMP14as was transfected into SW626 cells. Changes of cell proliferation, MT1-MMP protein expression, activities of MMP-2 and MMP-9, and cell invasion ability were detected by MTT assay, Western blot, optimized gelatin zymography, and matrigel in vitro invasion assay, respectively. RESULTS: Antisense MT1-MMP eukaryotic expression vector pMMP14as was constructed successfully. After 48-h transfection with pMMP14as, proliferation of pMMP14as-transfected SW626 cells was significantly lower than that of control cells. Compared with control cells, the expression of endogenous MT1-MMP protein in pMMP14as-transfected cells was decreased with a inhibition rate of 65.8%. The activation of proMMP-2 was remarkably inhibited, and the mean invasive cell percentage was (63.3+/-5.8)% in pMMP14as-transfected cells, which was far less than (97.6+/-7.5)% in control cells (P< 0.05). CONCLUSION: Both cell proliferation and invasive potential of SW626 cells were inhibited effectively by antisense MT1-MMP, suggesting that MT1-MMP may be a proper molecular target of anti-invasion therapy for human ovarian cancer.
The mechanisms of drug-resistance in human ovarian cancer cells have not been entirely clarified. The purpose of this study was to investigate whether LRP is involved in the resistance of ovarian cancer cell lines to cisplatin and its molecular mechanism. Human ovarian cisplatin-resistant cancer cell lines (A2780/DDP and COC1/DDP) and their parental cisplatin-sensitive cell lines (A2780 and COC1), alone or transfected with antisense LRP-specific oligonucleotides (ODN) or sense ODN, were treated with cisplatin to induce differentiation. Expression of LRP was examined by RT-PCR and Western blot analysis. The sensitivities of cells to cisplatin were assessed using sulforhodamine B (SRB) assay and flow cytometry, and the accumulation and efflux of cisplatin in the cells and isolated nuclei were examined by high performance liquid chromatographic (HPLC) assay. The expressions of LRP in A2780/DDP and COC1/DDP cells were higher than those in A2780 and COC1 cells and conferred resistance to cisplatin. Transfection of LRP AsODN into A2780/DDP and COC1/DDP cells down-regulated LRP expression and reversed the resistance phenotype. Levels of cisplatin accumulating in cells were increased by LRP-specific AsODN and anti-LRP monoclonal antibody. Isolated nuclei from A2780 and COC1 cells or A2780/DDP and COC1/DDP cells incubated with anti-LRP antibody contained more cisplatin than the nuclei of A2780/DDP and COC1/DDP cells not treated with anti-LRP antibody. Efflux of cisplatin was greater from the nuclei of A2780/DDP and COC1/DDP cells than those of A2780 and COC1 cells, and was inhibited by anti-LRP monoclonal antibody. Thus, LRP was involved in the resistance of ovarian cancer cells to cisplatin and has an important role in the transport of cisplatin both in exocytotic vesicles and between the nucleus and cytoplasm.
OBJECTIVE: To explore the feasibility of reverse effect of recombinant nm23H(1) adeno-associated virus (rAAV-nm23H(1)) in ovarian carcinoma metastatic orthotopic implantation nude model. METHODS: Using DNA recombination technique to construct AAV main plasmid pUF(1)-nm23H(1). rAAV-nm23H(1) and rAAV-Laz were produced by co-transfection of rAAV system in package cell 293 by phosphate-calcium deposit method, and then the transfection efficiency was measured. The titer was measured by dot hybridization. Ovarian carcinoma cell line SW626 was used in the establishment of the ovarian carcinoma orthotopic implantation nude model. The biologic feature of the model was observed and the expression of nm23H(1) in the tumor was measured by Western blot. Three groups of ovarian carcinoma orthotopic implantation nude model were applied by PBS (as control) (12 mice), rAAV-Laz (13 mice), rAAV-nm23H(1) (13 mice) intraperitoneally on the day 10 after transplantation. Then the effect of rAAV-nm23H(1) on survival and liver metastatic incident rates in models were observed. RESULTS: rAAV-nm23H(1) and rAAV-Laz were constructed and identified successfully. The titers were both 1 x 10(10) virus particles/ml. The transfection efficiency was 70%. The observation of biological feature showed the orthotopic implantation model was metastatic. The expression of nm23H(1) in AAV-nm23H(1) group was higher significantly than control and rAAV-Laz group (P < 0.05). Survival time of rAAV-nm23H(1) group was 136.67 days, compared with blank control group 106.67 days and rAAV-Laz group 107.06 days. Kaplan-Meier analysis showed rAAV-nm23H(1) group survived longer than control and rAAV-Laz group (P = 0.0051, P = 0.018 P < 0.05). The control and rAAV-Laz groups showed no statistically difference in survival time (P = 0.059 P > 0.05). The metastatic incident rate of control, rAAV-Laz and rAAV-nm23H(1) group was 75%, 61.5%, and 30.8% respectively, the rate of rAAV-nm23H(1) group was lower significantly than that of control and rAAV-Laz group (P = 0.03, P = 0.01). There was no significant difference between control and rAAV-Laz group in liver metastatic rate (P > 0.05). CONCLUSION: SW626 line which expressed lower level of nm23H(1) showed high-frequency metastasis properties, rAAV-nm23H(1) could reverse its metastasis in ovarian carcinoma orthotopic transplantation model.
OBJECTIVE: To examine the expression of the cyclin-dependent kinase inhibitor p27 in ovarian cancer multicellular spheroid (MCS) and explore the reversal effect of p27-antisense oligodeoxynucleotide (p27-ASON) on taxol resistance in ovarian cancer cell lines. METHODS: Three-dimensional culture was used to form MCS of human ovarian cancer cell lines A2780 and CAOV3. The MCSs were divided into 3 groups: MCSs transduced with p27-ASON or p27-sense oligodeoxynucleotide (p27-SON) by LipofectAMINE respectively and MCS without transduction. Monolayer A2780 and CAOV3 cells were cultured as controls. The cells were exposed to taxol of different concentrations (0.2, 2.0, 10.0, and 20.0 micro mol/L) for 24 hours. The expression of p27 in those cells was detected with Western blot and flow cytometry (FACS), and the subcellular distribution of p27 was detected by laser confocal microscopy before and after the experiment. The cell cycle profile and apoptosis were analyzed by FACS. The resistance to taxol was detected with trypan blue exclusion testing. RESULTS: Compared with that in monolayer cells, expression of p27 in MCS cells was significantly higher (P(A2780) = 0.011, P(CAOV3) = 0.024). The percentage of cells in G0-G1 phase was significantly higher in the MCS cells than in the monolayer cells, and the percentages of cells in S and G2-M phases were significantly lower in MCS cells than in monolayer cells. The apoptotic rate of the monolayer cells was significantly higher than those of MCS cells treated with taxol of the concentration of 20.0 micro mol/L (P(A2780) = 0.003, P(CAOV3) = 0.015). The apoptotic rate of p27-ASON/MCS was significantly higher than that of MCS (P(A2780) = 0.022, P(CAOV3) = 0.036). There was no significant difference of apoptotic rate between p27-SON/MCS and MCS (P(A2780) = 0.412, P(CAOV3) = 0.071). The monolayer A2780 and CAOV3 cells formed compact spheroids after three-dimensional culture. Cells transduced with p27-SON formed compact MCS too. However, cells tranduced with p27-ASON formed loose collections of cells easy to shatter. The expression of p27 in p27-ASON/MCSs was downregulated. CONCLUSION: The drug resistance of ovarian cancer MCS is related to upregulation of p27. P27-ASON reverses the resistance of ovarian cancer to taxol, thus increasing the chemotherapeutic sensitivity of ovarian cancer cells.
To evaluate the specific inhibition of antisense u-PAR on the u-PAR expressions in highly invasive cell subclones and to determine its blocking function in the invasion by those cells, a cDNA fragment of u-PAR obtained by RT-PCR was inserted into a plasmid vector named pcDNA3 in antisense orientation. Then the antisense u-PAR recombinant was transfected into highly invasive cell subclones. The u-PAR expression in neo-resistant cells was examined by RT-PCR and immunohistochemical assay. Compared to the control cells, the content of mRNA and protein of u-PAR in transfected cells decreased sharply, and the rate of inhibition was 53% and 73%, respectively, indicating that an antisense u-PAR might have played a specific inhibitory role in its expression in the cells, which may provide a good cell model for making further investigation of the inhibitory effects of the antisense u-PAR on invasion in highly invasive cell subclones of human prostate carcinoma.
To observe the inhibitory effects of an antisense u-PAR vector on invasion of highly invasive PC-3M cell subclones, the effects of the antisense u-PAR on activity of MMP-9 in those highly invasive cell subclones were detected by a quantitative RT-PCR and zymography. The monolayer invasion assay and colony formation assay in soft agar were used. And tumorigenesis rate and invasions by the cell subclones with or without the antisense u-PAR were observed in nude mice. It was found that in vitro growth of highly invasive PC-3M cell subclones transfected with the antisense u-PAR was declined, and the ability of anchorage-independent growth of those cell subclones was found decreased sharply, with the inhibiting rate becoming 79% and 60%, respectively. Although the antisense u-PAR didn't change MMP-9 gene transcription, they could inhibit the activation of MMP-9 of highly invasive PC-3M cell subclones. Moreover, the tumorigenesis rate of the cell subclones with the antisense u-PAR decreased and the growth of a neoplasm also slowed down. The t tests showed the difference between experimental and control groups was statistically significant (P < 0.01). The antisense u-PAR vector could not only inhibit the invasion ability of highly invasive PC-3M cell subclones in vitro but also restrain the growth of those cell subclones in vivo.
OBJECTIVE: To explore the role of apoptosis-associated genes and caspase-3 activity in cisplatin (DDP)-resistant human ovarian cancer cell lines. METHODS: The expressions of apoptosis-associated genes (bcl-2, bax, bcl-X(L) and bcl-X(S)) and the activity of caspase-3 were studied by reverse transcription-polymerase chain reaction (RT-PCR) and western blot in the cisplatin-resistant (A2780/DDP, COC1/DDP) and sensitive human ovarian cancer cells (A2780 and COC1). The apoptotic rates of A2780, COC1, A2780/DDP and COC1/DDP were measured with flow cytometry when treated with cisplatin. RESULTS: The mRNA expressions of bcl-2 and bcl-X(L) in A2780/DDP cells were 1.87 +/- 0.25 and 1.73 +/- 0.15, and significantly higher than those in A2780 cells (P < 0.05), which were 1.48 +/- 0.14 and 1.41 +/- 0.19 respectively. The protein expressions of bcl-2 and bcl-X(L) in A2780/DDP cells were 1.99 +/- 0.11 and 1.69 +/- 0.16, and significantly higher than those in A2780 cells (P < 0.05), which were 1.51 +/- 0.17 and 1.28 +/- 0.11 respectively. The expressions of bcl-2 and bcl-X(L) in COC1/DDP cells were also significantly higher than those in COC1 cells (P < 0.05). While there was no significant difference in expression of bax between A2780/DDP and A2780 as well as between COC1/DDP and COC1. No expression of bcl-X(S) was detected. When cells treated with different concentration of DDP, the caspase-3 activities, apoptotic rates and PARP expressions in A2780/DDP and COC1/DDP were significantly lower than those in A2780 and COC1 (P < 0.05), which showed dose-dependent (P < 0.05). CONCLUSION: Overexpression of anti-apoptotic genes and decrease of caspase-3 activity may relate to cisplatin resistance in human ovarian cancer cell lines.
BACKGROUND & OBJECTIVE: Cytotoxic anticancer drugs are less effective in killing tumor cells grown as multicellular spheroids than monolayer cell cultures. The aim of this study was to investigate the molecular mechanism of chemoresistance. METHODS: Ovarian cancer A2780, CAOV3 multicellular spheroids were obtained from three-dimensional culture. Expression of P-glycoprotein (P-gp) was determined using Western blot analysis and flow cytometry (FCM). The subcellular distribution of P-gp was also determined using laser confocal microscope. Reverse transcription-polymerase chain reaction (RT-PCR) was employed to detect the mdr1 mRNA of both monolayer cells and multicellular spheroids. Cell cycle profiles and apoptosis were also analyzed using FACS. The resistance was detected with trypan blue exclusion testing. RESULTS: Compared with control cells, no expression of P-gp was detected in monolayer cells, but expression of P-gp in aggregate cells was significantly elevated(P< 0.05). The mdr1 mRNA positive nodes were confirmed by RT-PCR in the aggregate cells. The percentage of cells increased in G(0)-G(1) phase and decreased in S and G(2)-M phase significantly in spheroids cells. Spheroids cells showed higher cell viability than monolayer cells (P(A2780)=0.003, P(CAOV3)=0.015). More apoptotic cells were induced by Taxol in MCS cells than in monolayer cells. CONCLUSION: Ovarian cancer A2780, CAOV3 multicellular spheroids cultures induced cell resistance to Taxol. High expression of P-gp was induced in ovarian multicellular spheroids and the cells were arrested in G(0)-G(1) phase.