Effect and mechanism of endoplasmic reticulum stress on cisplatin resistance in ovarian carcinoma
10.3760/cma.j.issn.0253-3766.2014.05.002
- VernacularTitle:内质网应激在卵巢癌顺铂耐药中的作用及其机制
- Author:
Jing TIAN
1
;
Xiaoming HU
;
Quanxin QU
Author Information
1. 300192,天津市第一中心医院妇产科
- Keywords:
Ovarian neoplasms;
Cisplatin;
Drug resistance,neoplasm;
Endoplasmic reticulum;
Stress
- From:
Chinese Journal of Oncology
2014;(5):324-328
- CountryChina
- Language:Chinese
-
Abstract:
Objective The study intended to investigate the effect and mechanism of endoplasmic reticulum stress on cisplatin resistance in ovarian carcinoma .Methods RT-PCR and Western blot were used to test the expression of mTOR and Beclin 1 mRNA and protein in ovarian cancer SKOV 3 cells after saquinavir induction .MTT assay was used to analyze the influence of saquinavir on cisplatin sensitivity in SKOV3 cells.Results The IC50 of SKOV3 cells was ( 5.490 ±1.148 ) μg/ml.After induced by Saquinavair 10μmol/L and 20μmol/L, the IC50 of SKOV3 cells was increased to (11.199 ±0.984) μg/ml and (14.906 ±2.015) μg/ml, respectively.It suggested that the sensitivity of ovarian cancer cells to cisplatin was decreased significantly (P=0.001).The expression of mTOR and Beclin1 mRNA and protein was significantly different among the five groups: the (Saquinavair +DDP) group of, Saquinavair group, LY294002 group, DDP group and control group(P<0.001).The expressions of mTOR and Beclin1 mRNA were highest in the ( Saquinavair +DDP ) group, 0.684 ±0.072 and 0.647 ±0.047, respectively;Secondly, the Saquinavair group , 0.577 ±0.016 and 0.565 ±0.037, respectively.The expressions of mTOR and Beclin1 proteins were also highest in the (Saquinavair+DDP) group, 0.624 ±0.058 and 0.924 ± 0.033, respectively, followed by the Saquinavair group , 0.544 ±0.019 and 0.712 ±0.024.3-MA inhibited the autophagy and restored cisplatin sensitivity in the SKOV 3 cells after Saquinavir induced ER stress ( P<0.001 ).Conclusions Saquinavir can effectively induce endoplasmic reticulum stress in SKOV 3 cells. Endoplasmic reticulum stress can decrease the sensitivity to cisplatin in SKOV 3 cells.The mechanism of the decrease of sensitivity to cisplatin in SKOV 3 cells may be that ERS regulates cell autophagy through the mTOR and Beclin1 pathways .ERS of tumor cells and autophagy may become a new target to improve the therapeutic effect of chemotherapy and to reverse the drug resistance in tumor treatment .
