Effects of celastrol on drug resistance of liver cancer cells through FAK/MEK/ERK signaling pathway
- VernacularTitle:雷公藤红素通过FAK/MEK/ERK信号通路对肝癌细胞耐药性的影响
- Author:
Xiaoming LUO
1
;
Xianmin ZENG
1
;
Liangren CAI
1
;
Xin ZHENG
2
Author Information
1. Dept. of Hepatobiliary Pancreatic Surgery，Hubei Third People’s Hospital，Wuhan 430033，China
2. Dept. of General Surgery，Wuhan Third Hospital，Wuhan 430060，China
- Publication Type:Journal Article
- Keywords:
celastrol;
liver cancer;
FAK/MEK/ERK kinase pathway;
malignant progression;
drug resistance
- From:
China Pharmacy
2024;35(20):2477-2481
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the effects of celastrol （CSL） on drug resistance of liver cancer cells. METHODS Human liver cancer lenvatinib （Len）-resistant cells Huh7/Len were constructed and divided into control group， CSL low-， medium- and high-concentration groups （1， 2.5， 5 μmol/L）， and CSL high-concentration+Zn27 [focal adhesion kinase （FAK） inhibitor] group （5 μmol/L CSL+2 nmol/L Zn27）， with 6 holes in each group. The proliferation （by absorbance） and cloning ability， apoptotic rate， the number of invasion cells and migration cells， the level of reactive oxygen species（ROS） as well as the protein expressions of phosphorylated FAK （p-FAK）， phosphorylated mitogen-activated protein kinase kinase （p-MEK）， phosphorylated extracellular signal-regulated kinase （p-ERK）， B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax） and caspase-3 were detected. RESULTS Compared with control group， cell absorbance， clone count， invasion count and migration count ， and the protein expressions of p-FAK， p-MEK， p-ERK and Bcl-2 were significantly reduced in the CSL low- ， medium- ， high- concentration groups； the apoptosis rate， ROS level， and protein expressions of Bax and caspase-3 were significantly increased， in a concentration-dependent manner （P＜0.05）. Compared with CSL high-concentration group， the changes of above indexes were all reversed significantly in CSL high-concentration+Zn27 group （P＜0.05）. CONCLUSIONS CSL can enhance oxidative stress， promote cell apoptosis， inhibit malignant progression and chemotherapy resistance of liver cancer cells， and its mechanism may be related to the inhibition of the FAK/MEK/ERK signaling pathway.
