Resistance Reversion of Rapamycin on Ovarian Cancer Cell Line SKOV3/DDP and Its Molecular Mechanisms
- VernacularTitle:雷帕霉素逆转卵巢癌细胞系SKOV3/DDP顺铂耐药及其机制探讨
- Author:
Guo-Cai XU
1
;
Dong-Yan WANG
;
Huai-Wu LU
;
Zhong-Qiu LIN
;
Bing-Zhong ZHANG
Author Information
1. 中山大学孙逸仙纪念医院妇产科
- Keywords:
ovarian cancer;
cisplatin-resistant;
rapamycin;
apoptosis
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2018;39(1):68-72
- CountryChina
- Language:Chinese
-
Abstract:
[Objective]To study the resistance reversion of rapamycin on ovarian cancer cell line SKOV3/DDP,and ex-plore its underlying molecular mechanisms.[Methods]MTT method was used to detect the cell toxicity,drug-resistant multi-ple and reversing multiple of cisplatin-resistant ovarian cancer cell line SKOV3/DDP;Western blot was used to detect the changes of Akt/mTOR Pathway induced by rapamycin.[Results]① MTT detected that when rapamycin concentration was 25,50,100,500 and 1 000 μg/L,its inhibition rates on cisplatin-resistant ovarian cancer cell line SKOV3/DDP were 4.48%,25.30%,35.86%,67.82%,81.43%.The concentration of 25 μg/L was selected to be the reversal concentration,be-cause its maximum rate was less than 5%.②The resistant index(RI)of cisplatin-resistant ovarian cancer cell line SKOV3/DDP was 2.21. ③ The reversal fold of 25 μg/L rapamycin on cisplatin-resistant ovarian cancer cell line SKOV3/DDP was 1.63.④Western blot results:After the addition of rapamycin,expression of p-mTOR and its downstream protein p-p70s6k in SKOV3 and SKOV3/DDP was significantly reduced. Meanwhile,there was a feedback increase in p-Akt.[Conclusions]Rapamycin has a reversal effect on cisplatin-resistant ovarian cancer cell line SKOV3/DDP. Its reversal mechanism may be inhibiting the cell proliferation and promoting cell apoptosis by depressing the expression of p-mTOR and its downstream pro-tein p-p70s6k in Akt/mTOR Pathway.