摘要
目的探讨塞来昔布联合顺铂对人卵巢癌顺铂耐药细胞株COC1/DDP生长和凋亡的影响及其机制.方法采用MTT法检测不同浓度(0、0.625、12.5、25、50及100μmol/L)塞来昔布对COC1/DDP细胞生长的影响,计算出24、48及72 h的IC50.将对数生长期的COC1/DDP细胞随机分为对照组(未做处理)、顺铂组(给予2μg/ml顺铂)、塞来昔布组(给予25μg/ml塞来昔布)及联合组(给予25μg/ml塞来昔布+2μg/ml顺铂).MTT法检测各组细胞的生长情况,FCM检测各组细胞的凋亡情况,Western blot检测各组细胞中增殖细胞核抗原(Ki67)、细胞周期素D1(CyclinD1)、生存素(Survivin)和B淋巴细胞瘤-2基因(Bcl-2)蛋白的表达.结果塞来昔布能够呈时间-浓度依赖性抑制COC1/DDP细胞生长,其在24、48和72 h的IC50分别为47.05、25.86和16.11μmol/L.与对照组相比,顺铂组、塞来昔布组和联合组中COC1/DDP细胞的OD值以及Ki67、CyclinD1、Survivin及Bcl-2蛋白的表达水平均显著降低,凋亡率均显著升高;但顺铂对COC1/DDP细胞的作用较弱,塞来昔布对COC1/DDP细胞的作用较强,联合用药能够增强两者对COC1/DDP细胞的作用且高于两者之和.结论塞来昔布联合顺铂能够协调抑制COC1/DDP细胞生长并诱导细胞凋亡,降低COC1/DDP细胞对顺铂的耐药性,其分子机制可能与下调Ki67、CyclinD1、Survivin及Bcl-2蛋白表达有关.
Objective To investigate the effect of celecoxib combined with cisplatin on the growth and apoptosis of cisplatin resistant cell line COC1/DDP in human ovarian cancer and its mechanism. Methods The effects of different concentrations( 0,0. 625,12. 5,25,50 and 100 μmol/L) of celecoxib on the growth of COC1/DDP cells were detected by MTT,and the IC50 of 24,48 and 72 h was calculated. The COC1/DDP cells in logarithmic growth phase were randomly divided into control group( untreated),cisplatin group( treated with2 μg/ml cisplatin),celecoxib group( treated with 25 μg/ml celecoxib) and combined group( treated with 25 μg/ml of celecoxib and 2μg/ml of cisplatin). The growth of cells in each group was detected by MTT method,the apoptosis of cells in each group was tested by FCM,and the expressions of Ki67,Cyclin D1,Survivin and Bcl-2 proteins in each group weremeasured by Western blot. Results The growth of COC1/DDP cells in a time dependent manner could be inhibited by Celecoxib,and the IC50 of 24,48 and 72 h were 47. 05,25. 86 and16. 11 μmol/L respectively. Compared with the control group,the OD values and expression levels of Ki67,Cyclin D1,Survivin and Bcl-2 proteins of COC1/DDP cells in cisplatin group,celecoxib group and combination group were significantly decreased,and the apoptosis rates were significantly increased;but the effect of cisplatin on COC1/DDP cells was weaker,and the effect of celecoxib on COC1/DDP cells was stronger,while the combination of the two drugs could enhance the effect of the two drugs on COC1/DDP cells and was higher than the sum of the two drugs. Conclusion Celecoxib combined with cisplatin can coordinate the inhibition of COC1/DDP cell growth and induce cell apoptosis,and relieve the resistance of COC1/DDP cells to cisplatin,and its molecular mechanism may be related to down-regulation of Ki67,Cyclin D1,Survivin and Bcl-2 protein expression.
作者
简露
陈林
陈俞先
李涛
JIAN Lu;CHEN Lin;CHEN Yu-Xian(Pharmaceutical Department,Department of Clinical Pharmacy,West China Hospital,Sichuan University,Chengdu,Sichuan 610041,China)
出处
《中国妇幼保健》
CAS
2019年第13期3080-3083,共4页
Maternal and Child Health Care of China
基金
四川省食品药品监督管理局课题研究项目(H170416)
关键词
塞来昔布
顺铂
卵巢癌
耐药
细胞生长
凋亡
celecoxib
cisplatin
ovarian cancer
drug resistance
cell growth
apoptosis
