Dipyridyl pyrrolidine inhibits MDA-MB231 breast cancer cell cycle by inhibiting AKT-mTOR
10.11665/j.issn.1000-5048.20180613
- VernacularTitle:二吲哚吡啶基吡咯烷通过抑制AKT-mTOR阻滞MDA-MB231乳腺癌细胞周期
- Author:
Liang YAN
1
;
Jiawei ZAN
;
Zunyong FENG
;
Jinzhu MA
;
Lei XU
;
Yi WANG
Author Information
1. 皖南医学院活性生物大分子安徽省重点实验室
- Publication Type:Journal Article
- Keywords:
dipyridyl pyrrolidine;
breast cancer;
MDA-MB231 cells;
cell cycle
- From:
Journal of China Pharmaceutical University
2018;49(6):718-724
- CountryChina
- Language:Chinese
-
Abstract:
To investigate the induction of cell cycle arrest of human breast cancer MDA-MB231 cells by Di-indolyl pyrrolidine(DIPRD), a pyrrolidine-derived spirooxindoles compounds. The cytotoxic effect of DIPRD on MDA-MB231 cells was detected by CCK-8 method. The cell cycle arrest of MDA-MB231 cells was detected by DAPI/EdU double-staining. Phosphorylation levels of AKT, mTOR, apoptosis-related proteins p53, MDM2, and DNA repair enzyme PARP levels were detected by Western blot. DIPRD inhibited the viability of MDA-MB231 cells by downregulating the number of EdU-positive cells, increase G1 phase and reduce cell number in S/G2 phase, down-regulated the p-AKT(Ser473), p-mTOR, p-p53, cyclin D1, CDK4, and the upregulated the p-AKT(Thr308), p-MDM2 and Cleaved-PARP levels were detected in a dose-dependent manner at 12. 5, 25, and 50 mg/mL. DIPRD may play a role in cell cycle arrest through AKT signaling pathway and induce cell apoptosis.
