A novel chalcone derivative C13 inhibits the growth of human gastric cancer cells through suppressing ErbB4/PI3K/AKT signaling pathway
10.16438/j.0513-4870.2023-1262
- VernacularTitle:一种新型查耳酮衍生物C13通过ErbB4/PI3K/AKT信号通路抑制人胃癌细胞的生长
- Author:
Peng TAN
;
Yun-feng ZHANG
;
Long-yan WANG
;
Hui-ming HUANG
;
Fei WANG
;
Xue-jiao WEI
;
Zhu-guo WANG
;
Jun LI
;
Zhong-dong HU
- Publication Type:Research Article
- Keywords:
chalcone derivative C13;
human gastric cancer cell;
proliferation;
apoptosis;
ErbB4/PI3K/AKT signaling pathway
- From:
Acta Pharmaceutica Sinica
2024;59(4):957-964
- CountryChina
- Language:Chinese
-
Abstract:
3ʹ-Hydroxy-4ʹ-methoxy-2-hydroxy-5-bromochalcone (hereinafter referred to as C13) is a novel chalcone derivative obtained in the process of structural modification of DHMMF, the antitumor active compound of Resina Draconis, in our laboratory. In this study, we investigated the effects of C13 on the proliferation and apoptosis of human gastric cancer HGC-27 and AGS cells and its potential mechanism of action. Firstly, through methyl thiazolyl tetrazolium (MTT), colony formation assay, and 5-ethynyl-2'-deoxyuridine (EdU) staining, we found that C13 inhibited the proliferation ability of human gastric cancer HGC-27 and AGS cells. Using flow cytometry and Western blot, it was found that C13 induced apoptosis in human gastric cancer HGC-27 and AGS cells, and up-regulated the protein level of cleaved poly ADP-ribose polymerase (cleaved-PARP). The results of RNA sequencing analysis showed that the Erb-b2 receptor tyrosine kinase 4/phosphoinositide 3-kinases/AKT (ErbB4/PI3K/AKT) signaling pathway may be involved in anti-gastric cancer activity of C13. Finally, the results of immunoblotting assay showed that C13 treatment down-regulated the protein levels of ErbB4 and phospho-ErbB4, as well as down-regulated the phosphorylation levels of PI3K and AKT in human gastric cancer HGC-27 and AGS cells, which verified the results from RNA-seq analysis. In conclusion, C13 inhibited the proliferation and induced apoptosis of human gastric cancer cells, which may be related to the down-regulation of ErbB4/PI3K/AKT signaling pathway. This study may provide a candidate drug for the treatment of gastric cancer.
