【摘要】 目的　探讨顺铂 (DDP)、维拉帕米 (VP)及 3′ 酮基 去甲基苏氨酸 1 缬氨酸 2 环孢菌素(PSC 833)诱导卵巢癌细胞凋亡的作用机理。方法　以人卵巢癌亲代细胞株COC1及其耐DDP亚细胞株COC1/DDP为材料 ,根据所加药物的不同分为DDP组、VP组、PSC 833组、DDP联合VP组、DDP联合PSC 833组和对照组 ,计算各组细胞生长抑制率、细胞凋亡率同时进行细胞周期分析。结果　DDP联合VP组和DDP联合PSC 833组COC1、COC1/DDP的细胞生长抑制率均增高 ,两组COC1的细胞生长抑制率分别为 48.5 6 %和 47.86 %、两组COC1/DDP的细胞生长抑制率分别为 39.47%和 37.81% ,量效曲线均下移 ,两组分别与DDP组比较 ,差异均有显著性 (P <0 .0 5 )。DDP引起S期细胞比例增高 ,当DDP浓度为 1.0 μg/ml时 ,COC1细胞S期比例最高达 99.6 7% ,而DDP浓度为 2 .0 μg/ml时 ,S期比例最低降至 33.6 1% ,S期细胞大量凋亡 ;COC1、COC1/DDP的细胞凋亡率不同 ,DDP(0 .5～ 2 .0 μg/ml) +PSC833(0 .30 μg/ml)时的细胞凋亡率明显提高 ,与对照组比较 ,差异均有显著性 (P均 <0 .0 5 )。 结论　VP、PSC 833有增敏作用 ,PSC 833能增强DDP诱导COC1/DDP细胞凋亡的作用。诱导细胞凋亡是DDP作用于COC1、COC1/DDP细胞的机理之一 ,获得性耐药与细胞凋亡耐受有关。更多还原

【Abstract】 Objective To study the pharmaceutical mechanisms of cisplatin(DDP), verapamil(VP) and SDZ PSC833, and the mechanism of developing acquired drug resistance. Methods Two ovarian carcinoma cell lines——one sensitive (COC 1) and the other resistant (COC 1/DDP) to cisplatin were used in this study. The cell viability was measured by trypan blue dye exclusion assay. The apopotic cells were observed and distinguished by light and electron microscopy, and comet assay. Flow cytometry was used to measure the cell cycle. Six groups were set up according to drug(s) delivered: DDP, VP, SDZ PSC833, DDP and VP, DDP and SDZ PSC833, and control group. Results (1) VP or SDZ PSC833 enhanced cytotoxicity of DDP (q>1, P <0.01). (2)The most prominent effect of DDP on cell cycle kinetics was a slowdown in S phase transit during which cells undergo apoptosis ( P <0.05). (3) COC 1 and COC 1/DDP cells had different rates of apoptosis when DDP added. SDZ PSC833 enhanced apoptosis of COC 1/DDP cells induced by DDP. Conclusions VP and SDZ PSC833 increase sensitivity of the cell lines to DDP. SDZ PSC833 enhances apoptosis induced by DDP.Induction of apoptosis is one of the pharmaceutical mechanisms of DDP, and acquired drug resistance is associated with resistance to apoptosis. The most prominent effect of DDP on cell cycle kinetics is a slowdown in S phase transit and apoptotic cells are at S phase.更多还原