OSTP-DDP靶向抑制卵巢癌A2780细胞生长作用的研究

The inhibitory effect of OSTP-DDP on the growth of ovarian cancer A2780 cells

目的研究卵巢癌特异性结合肽(ovarian cancer specific targeting peptide,OSTP)与顺铂(cis-dichlorodiamineplatinum,DDP)偶联物(OSTP-DDP)对卵巢癌A2780细胞的靶向抑制作用。方法化学合成OSTP-DDP,体外培养卵巢癌A2780细胞,采用CCK-8法分别检测OSTP-DDP和DDP对卵巢癌A2780细胞的生长抑制作用;通过Annexin V-FITC凋亡试剂盒分别检测OSTP-DDP和DDP对卵巢癌A2780细胞的周期和凋亡作用。结果通过质谱分析和高效液相色谱(HPLC)分析,提示成功合成OSTP-DDP。CCK-8法检测显示,OSTP-DDP与DDP分别以不同浓度(10、20、40、80、160、320μmol·L^(-1))处理卵巢癌A2780细胞24、48、72 h后,均可对该细胞的生长起到抑制作用,且呈时间、浓度依赖性。且OSTP-DDP的作用强于DDP(P<0.05),提示OSTP-DDP具有靶向抑制细胞生长作用。流式细胞术检测结果显示,经OSTP-DDP和DDP处理后,细胞周期均被阻滞于G_1期,作用72 h后,OSTP-DDP对卵巢癌A2780细胞的周期抑制作用强于DDP,差异具有统计学意义(P<0.05)。作用24、48、72 h后,OSTP-DDP对卵巢癌A2780细胞凋亡的作用强于DDP(P<0.01)差异具有统计学意义,提示OSTP-DDP具有较强的靶向诱导细胞凋亡作用。结论 OSTP-DDP对卵巢癌A2780细胞的生长具有靶向抑制作用,OSTP作为化疗药物靶向载体治疗卵巢癌有良好的应用前景。

Aim To study the growth inhibitory effect of the conjugate(ovarian cancer specific targeting peptide and cisplatin,OSTP-DDP) that targeting ovarian cancer cells A2780.Methods Using chemical method to synthesize OSTP-DDP,ovarian cancer cells A2780 were cultured in vitro,using CCK-8 method(Cell Counting Kit-8) to detect the growth inhibitory effect of ovarian cancer A2780 cells,which were disposed by OSTP-DDP and DDP.Annexin V-FITC was used to detect the cycle and apoptosis effect of ovarian cancer A2780 cells which were disposed by OSTP-DDP and DDP.Results According to the mass spectrometry and the high performance liquid chromatography(HPLC) analysis,OSTP-DDP was proved to synthesize successfully.CCK-8 assay showed that both OSTP-DDP and DDP could play the growth inhibitory effect and showed a concentration-dependent manner when cells were treated in different concentrations(10,20,40,80,160,320 μmol·L^(-1)) respectively after 24 h,48 h,72 h.And the effect of OSTP-DDP was stronger than DDP(P<0.05),indicated OSTP-DDP had targeted cytostatic effect.The result of the flow cytometry showed that cell cycle was mostly arrested in G_1 phase after 72 h treated by OSTP-DDP and DDP,the inhibitory effect of OSTP-DDP was stronger than DDP(P <0.05).The apoptosis effect of OSTP-DDP was stronger than DDP(P <0.01),suggested that OSTP-DDP had a stronger targeting apoptosis-inducing effect.Conclusion OSTP-DDP has the targeting growth inhibitory effect on the ovarian cancer cell A2780,OSTP as a chemotherapeutic drug targeting vector has a great prospect to treat ovarian cancer.