Effects of celastrol on drug resistance of liver cancer cells through FAK/MEK/ERK signaling pathway
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.
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