Celastrol inhibits PAK1 kinase and inhibits the proliferation of pancreatic cancer cells
10.16438/j.0513-4870.2019-0580
- VernacularTitle:雷公藤红素通过抑制PAK1抗胰腺癌作用及其机制研究
- Author:
Ling-xia ZHU
1
;
Xiao-yan SUN
1
;
Jiao CHEN
1
;
Xue-ting CAI
1
;
Peng CAO
1
Author Information
1. Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing 210028, China; School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
- Publication Type:Research Article
- Keywords:
p21-activated kinase 1;
pancreatic neoplasms;
tripterine;
proliferation;
apoptosis
- From:
Acta Pharmaceutica Sinica
2020;55(1):60-66
- CountryChina
- Language:Chinese
-
Abstract:
The p21-activated kinase 1 (PAK1) is a member of the P21-activated protein kinase family that plays an important role in the proliferation and on cogenesis of pancreatic cancer. PAK1 is an important target for the treatment of pancreatic cancer. At present, akinase inhibitor targeting PAK1 is still in the preclinical research stage. Therefore, screening for new PAK1 kinase inhibitors is of great significance. In this study the natural compound celastrol was found to have a significant inhibitory effect on PAK1, with an IC50 value of 3.614 μmol·L-1. Molecular docking results showed that celastrol had good binding to PAK1. An MTT assay indicated that celastrol inhibited the proliferation of pancreatic cancer cells BxPC-3 and PANC-1. Mechanistic studies revealed that the inhibition of pancreatic cancer cells by celastrol was reversed by PAK1 siRNA. Celastrol inhibited PAK1 and the subsequent activation of downstream signaling pathways, thereby activating apoptosis signaling pathways and triggering apoptosis in pancreatic cancer cells. These findings suggested that celastrol induced apoptosis in pancreatic cancer cells by suppressing the PAK1 kinase signaling pathway and has potential value for the treatment of pancreatic cancer.
