The Effect Of Oxaliplatin And Capecitabine, Docetaxel On Human Ovarian Cancer Cell Lines COC1

Objective:To observe the effects of Oxaliplatin and Capecitabine, Docetaxel on Human Mucinous Ovarian Cancer Cells COC1 in vitro.and investigate the mechanism.To compare the effect of OXA+CAP vs second line(OXA+DTX) chemotrapy on COC1 cell lines.To provide the theroy foundation that if it can use for the chemotherapy of human ovary cancer.Method:1)WST-1 assay was used to analyze the growth-inhibition effects of single drug and combination drugs of different concentrations of capecitabine (CAP),oxaliplatin (OXA),and docetaxel(DTX) on human ovarian cancer COC1 cell line.2)Interaction between OXA and DTX,CAP on human ovarian cancer COC1 cell was evaluated using the combination index (CI) method based on the median effect principle.3)Distribution of cell cycle and apoptotic rate were analysed using flow cytometry(FCM).Results:1)CAP,OXA and DTX alone or in combination effectively inhibited the growth of COC1 ovarian cancer cells in a concentration-dependent manner at certain range of concentrations. Among the monotherapy groups, CAP group had the lowest IC50, and the strongest inhibitory effect (P<0.01). Among the combined Groups, OXA combined CAP group had lower IC50 and stronger inhibitory effect than the groupOXA combined DTX's (P<0.01).2)At 24h,OXA and CAP had antagonistic effect when Fa< 0.4 and synergistic effect when Fa>0.4 on inhibiting growth of human ovian cancer COC1 cell line,OXA and DTX had antagonistic effect when Fa< 0.5 and synergistic effect when Fa>0.5 on inhibiting growth of human ovian cancer COC1 cell line.3) Flow cytometry analysis showed that:Among the monotherapy groups, the apoptosis rate of DTX group (19.54%) was higher than either OXA(14.52%) or CAP (12.51%) group,p<0.05.The apoptosis rate of OXA combined with CAP (24.86%) was higher than either one used separately(p<0.01).The apoptosis rate of OXA combined with DTX(19.54%) was higher than either one used separately (p<0.01).The apoptosis rate of OXA+CAP group was signi-ficantly higher than OXA+DTX group(P<0.01).4) The cell cycle showed that:OXA and CAP,DTX alone can retard cell cycle at G0/Gl(46.45%),S(75.41%), G2/M (10.26%) phase respectively.The rate of S phase (66.40%) and G2/M(5.22%) retarded by OXA+CAP was increasing significantly, suggesting that capecitabine combined with oxaliplatin can arrest cell cycle at S phase.The rate of G2/M phase(25.91%) retarded by OXA+DTX was significantly higher than either one used separately,which suggesting that OXA had synergistic effect on DTX to promote cell arrest at G2/M phase.Conclusion:1)oxaliplatin and capecitabine, docetaxel alone or in combination effectively inhibited the growth of COC1 ovarian cancer cells in a time and concentration-dependent manner.especially in a time depen-dent manner.2) capecitabine's antitumor mechanism may be related to the detention of S phase and induction of tumor cell apoptosis.3) The inhibition of oxaliplatin combined capecitabine to COC1 cell line were significantly higher than the second line chemothrapy(oxaliplatin combined docetaxel). oxaliplatin was synergetic with capecitabine at high concentration (≥IC50), suggesting that in combination therapy,choosing their IC50 respectively may get better efficacy of ovarian mucinous adenocarcinoma.