GPER inhibitor increases tamoxifen-induced apoptosis in T-47DTR-resistant cells
- Author:
Min-Qin ZHANG
1
;
Min ZHANG
1
;
Min-Qin ZHANG
2
;
Yu-Xuan SONG
2
;
Shuang-Qin FAN
2
;
Shuang REN
2
;
Yue ZHANG
2
;
Yan CHEN
2
;
Xiang-Chun SHEN
2
;
Tong-Zheng LIU
2
;
Min ZHANG
2
Author Information
- Publication Type:Journal Article
- Keywords: apoptosis; breast cancer; drug resistance; G15; GPER; tamoxifen
- From: Chinese Pharmacological Bulletin 2023;39(1):96-100
- CountryChina
- Language:Chinese
- Abstract: Aim To study the effect of G protein-coupled estrogen receptor(GPER)inhibitor G15 on the sensitivity of breast cancer tamoxifen-resistant cells to T-47DTR. Methods Experiments were carried out with 4-hydroxytamoxifen(4-OHT),the active form of tamoxifen in vivo. The sensitivity of tamoxifen-resistant breast cancer cell line T-47DTR and its parental cell line T-47D to tamoxifen was detected by MTT assay; the expression of GPER protein was analyzed by plasma separation of inhibitor G15; the effect of 4-OHT combined with G15 on the apoptosis of T-47DTR cells was analyzed by flow cytometry AnnexinV-FITC/PI double staining; the expression levels of apoptosis-related proteins Bax,Bcl-2,caspase-3,cleaved caspase-3,caspase-9,cleaved caspase-9 were analysed by Western blot. Results(1)Compared with the parental cell T-47D,the resistance of T-47DTR-resistant cells to 4-OHT was significantly enhanced.(2)When 4-OHT(2 μmol·L-1)was administered,the membrane distribution of GPER increased,indicating that GPER was activated in T-47DTR-resistant cells compared with the control group; Compared with OHT,the use of G15(5 μmol·L-1)and OHT significantly reduced the expression of GPER.(3)GPER inhibitor G15 could increase the apoptotic rate of T-47DTR-resistant cells while down-regulating the anti-apoptotic protein Bcl-2 and up-regulating the expression of pro-apoptotic proteins Bax,cleaved caspase-3,cleaved caspase-9. Conclusions The GPER inhibitor G15 increases the apoptosis of T-47DTR cells and restores the sensitivity of drug-resistant cells to tamoxifen.
