In vitro anti-tumor effects and mechanisms of a novel c-KIT inhibitor PN17-1 on gastrointestinal stromal tumor GIST-882 cells
10.16438/j.0513-4870.2024-0779
- VernacularTitle:新型c-KIT抑制剂PN17-1对胃肠道间质瘤GIST-882细胞的体外抗肿瘤作用及机制研究
- Author:
Ji-wei SHEN
1
;
Shuang WU
2
;
Jun LI
2
;
Yun-peng ZHOU
1
;
Ye CHEN
1
;
Ju LIU
1
Author Information
1. College of Pharmacy of Liaoning University, Shenyang 110036, China; Small Molecular Targeted Drug R&D Engineering Research Center of Liaoning Province, Shenyang 110036, China
2. College of Pharmacy of Liaoning University, Shenyang 110036, China
- Publication Type:Research Article
- Keywords:
gastrointestinal stromal tumor;
c-KIT inhibitor;
GIST-882 cell;
proliferation;
apoptosis
- From:
Acta Pharmaceutica Sinica
2025;60(2):379-387
- CountryChina
- Language:Chinese
-
Abstract:
In recent years, gastrointestinal stromal tumors (GIST) have increased incidence and mortality, and most GIST is caused by the activation mutation of the c-KIT gene. Therefore, c-KIT has become a promising therapeutic target of GIST. At present, the drugs approved for the treatment of GIST including imatinib, sunitinib, regorafenib and ripretinib, are mostly prone to developing resistance and accompanied by various degrees of adverse reactions. Therefore, there is an urgent need to develop new c-KIT inhibitors to solve the problem of resistance. In this study, we investigated the anti-tumor effect of a novel c-KIT inhibitor PN17-1 on gastrointestinal stromal tumor GIST-882 cells in vitro. We found that PN17-1 significantly inhibited the proliferation, colony formation and migration ability of GIST-882 cells, and significantly downregulated the protein expression levels of p-c-KIT and its downstream signals p-AKT, p-STAT5 and p-ERK in GIST-882 cells. In addition, PN17-1 induced apoptosis in GIST-882 cells, and the apoptosis may be mainly related to the mitochondrial-dependent endogenous pathway. In conclusion, the novel c-KIT inhibitor PN17-1 is a promising anti-GIST drug, and this study provides new ideas for further development of c-KIT inhibitors in the future.
