摘要
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SK-OV3/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。
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. Results NDP 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. Conclusion NDP can in hibit 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.
出处
《肿瘤防治研究》
CAS
CSCD
北大核心
2012年第10期1216-1220,共5页
Cancer Research on Prevention and Treatment
基金
广西自然科学基金资助项目(0832136)
广西壮族自治区卫生厅资助课题(S200803)
