Their Experimental Study Of Cisplatin And SN-38 Anti-tumor Roles In The Cervical Cancer

Objective Cervical cancer remains a major worldwide health. Inhibitors of topoisomerase I have proven to be among the most promising new classes of antineoplatic agents introduce into the clinic in recent years. CPT-11 is one of the most widely used camptothecin analogues and is converted to form the active metabolite SN-38. In vitro cytotoxicity of SN-38 was evaluated using two human cervical cancer cell lines(HeLa and Siha). To study apoptosis by SN-38 on cervical cancer cell lines HeLa and Siha and those mechanisms in vitro.Methods Cell growth inhibition of SN-38 on HeLa and Siha cells were analyzed by MTT assay; Cell apoptosis was measured with cytometry and Hoechst33258 when treated with SN-38. The protein expressions of p53, p21, Bax, Bcl-2, Akt and p-Akt were studied by western blot.Results SN-38 inhibited proliferation in a time and dose-dependant manner. Sub-G1 peak by flow cytometry showed significant in the experimental group than the control; Hoechst33258 showed apoptosis induced by SN-38; Western Blot showed SN-38 down-regulateing protein expression of p-Akt and increased protein expression of p53 and p21, but it had no effects on protein expression of Bax, Bcl-2 and Akt.Conclusion Transfection of the full-length akt cDNA into HeLa and SiHa cells resulted in the reduction of the cytotoxic effect of SN-38, indicating that inhibition of the Akt pathway played an important role in exhibition of SN-38-mediated cytotoxic effects. Results from this study suggest that the SN-38 exhibits its cytotoxic effects by activating the p53-mediated apoptosis and down-regulating the Akt survival signaling pathway.Objective: To study apoptosis by cisplatin on cervical cancer cell line Hela and its mechanism in vitro.Methods: Cell growth inhibition of cisplatin on Hela was analyzed by MTT assay; Cell apoptosis were measured with cytometry and Hoechst33258 when treated with cisplatin. The effects of cisplatin on transcription of E6 were analyzed by RT-PCR; The protein expressions of E6, p53, p21, Bax and Bcl-2 were studied by western blot.Results: Cisplatin inhibited proliferation in a time and dose-dependant manner. Sub-G1 peak by flow cytometry showed significant in the experimental group than the control; Hoechst33258 showed apoptosis induced by cisplatin; RT-PCR showed cisplatin decreased transcription of HVP E6; Western Blot showed cisplatin decreased protein expression of E6 and increased protein expression of p53, p21and Bax as well as had no effects on protein expression of Bcl-2.Conclusion: Cisplatin can induce apoptosis in Hela cells through the suppression of HPV E6 to restore the function of p53 in order to induce apoptosis to kill the tumor cell.Objective: To study cell cycle arrest and apoptosis by cisplatin on cervical cancer cellline Siha and its mechanism in vitro.Methods: Cell growth inhibition of cisplatin on Siha was analyzed by MTT assay;Cell apoptosis were measured with DNA cytofluorometry and Hoechst33258 andDNA electrophoresis when treated with cisplatin. Cell cycle arrest were analyzed bycytometry. The protein expressions of E6, p53 and p21 were studied by western blot.Results: Cisplatin inhibited proliferation in a time and dose-dependant manner.Sub-G1 peak by flow cytometry showed significant in the experimental group thanthat in the control; Hoechst33258, DNA ladder and cytomytry showed apoptosisinduced by cisplatin; Cisplatin can cause G₂-M cell cycle arrest. Western blot showedcisplatin decreased protein expression of E6 and increased protein expression of p53and p21.Conclusion: Cisplatin can induce cycle arrest and restore the function of p53 toinduce apoptosis in Siha cells to kill the tumor cell.