奈达铂体外诱导人卵巢癌顺铂耐药细胞凋亡的机制

目的探讨研究奈达铂（NDP）体外对人卵巢癌顺铂原发耐药细胞株SKOV3和继发耐药株SKOV3/DDP的抑制作用及其机制。方法采用MTT法检测体外不同时间不同浓度的NDP对SKOV3及SKOV3/DDP细胞的杀伤作用，计算半数抑制浓度(IC50);流式细胞术(FCM)测定给药前后细胞凋亡率及周期分布变化;半定量PCR分析凋亡基因Bcl-2,Bax,caspase-3,caspase-9及反应肿瘤细胞侵袭力的基因MMP-2的表达变化。结果NDP能明显抑制SKOV3及SKOV3/DDP生长，呈时间-剂量依赖性;流式结果显示随时间、浓度增加，SKOV3和SKOV3/DDP细胞凋亡明显增加，S期细胞的比例增加，差异均有统计学意义（P<0.05）。与对照组相比，Bcl-2、MMP-2表达减少，Bax,caspase-3,caspase-9表达增加。结论NDP可抑制SKOV3和SKOV3/DDP细胞增殖，其机制可能与诱导细胞凋亡，细胞S期阻滞，下调Bcl-2及上调Bax,caspase-3,caspase-9的表达有关;同时可下调MMP-2的表达，有利于降低卵巢癌细胞的侵袭力。

Nedaplatin Induced Apoptosis in Human Ovarian Cancer Cisplatin-resistant Cell Lines in vitro and Investigated Its Mechanism

Objective
To study inhibition of nedaplatin(NDP) on human ovarian cancer cell lines SKOV3 with intrinsic cisplatin-
resistance and SKOV3/DDP with acquired cisplatin-resistance and investigate its mechanism.Methods MTT assay was
used to evaluate the inhibition in different concentration and time of NDP treatment on SKOV3 and SKOV3/DDP
cells,then calculated inhibitory concentration(IC50).Cell apoptosis and cycle were detected by flow cytometry
(FCM).The changes of Bcl-2,Bax,caspase-3,caspase-9,MMP-2 in mRNA levels were quantified by RT-PCR.ResultsNDP
inhibited the growth of SKOV3 and SKOV3/DDP cells significantly in time and dose-dependent manner.The result from
FCM showed that apoptotic rate and the percentage of S-phase cells tend to increase in time and concentration of
nedaplatin dependent manner(P<0.05).Compared with control groups,there were a decrease in Bcl-2 and MMP-2 mRNA
expression,but an increase in Bax,caspase-3 and caspase-9.ConclusionNDP can inhibit proliferation of SKOV3 and
SKOV3/DDP cells.The effect may be ascribed to inducing cell apoptosis，the S-phase arrest and the down-regulation
of Bcl-2,MMP-2 expression,up-regulation of Bax,caspase-3 and caspase-9 expression.NDP can suppress MMP-2
expression,so it maybe can reduce invasion force of ovarian cancer.