Effects of c-Jun N-terminal kinase inhibitor D-JNKI1 on proliferation, invasion and apoptosis of human hepatocellular carcinoma HepG2 cells and its mechanism
10.13200/j.cnki.cjb.004448
- VernacularTitle:c-Jun氨基末端激酶抑制剂D-JNKI1对人肝癌HepG2细胞增殖、侵袭、凋亡的影响及其作用机制
- Author:
LI Shuanghui
- Publication Type:Journal Article
- From:
Chinese Journal of Biologicals
2025;38(03):302-311
- CountryChina
- Language:Chinese
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Abstract:
Objective To investigate the effects of c-Jun N-terminal kinase(JNK) inhibitor D-JNKI1 on proliferation,invasion and apoptosis of human hepatocellular carcinoma HepG2 cells and its mechanism,so as to provide reliable experimental evidence for further study on the preventive and therapeutic effects of JNK inhibitor on hepatocellular carcinoma.Methods HepG2 cells were treated with 0,5,10 and 20 μmol/L D-JNKI1 for 24,48 and 72 h separately,and detected for the proliferation activity by CCK-8 assay.HepG2 cells were treated with 10 μmol/L D-JNKI1 for 0,24,48 and 72 h,and the control group(100% DMSO) was set.The effects of D-JNKI1 on migration,invasion and epithelial-mesenchymal transition abilities of HepG2 cells were detected by scratch test,Transwell invasion test and Western blot respectively.The effect of D-JNKI1 on apoptosis of HepG2 cells was measured by TUNEL and Hoechst staining.The mitochondrial membrane potential of HepG2 cells was detected by JC-1 staining,and the content of ROS in HepG2 cells was detected by DCFA-DA method.Western blot was used to determine the expression levels of apoptosis pathway related factors and MAPK signaling pathway key molecules in HepG2 cells.After intraperitoneal injection of D-JNKI1 in nude mice,HepG2 cell suspension was inoculated through the right armpit,and the tumor volume was measured every week.Six weeks after inoculation of HepG2 cells,the nude mice were sacrificed by cervical dislocation,and the tumor mass was weighed.The expression levels of apoptosis pathway related factors were detected by Western blot.Results D-JNKI1 effectively inhibited the proliferation,invasion and migration,and epithelial-mesenchymal transition process of HepG2 cells,promoted apoptosis of HepG2 cells through endogenous and exogenous apoptotic pathways,reduced mitochondrial membrane potential and ROS level in the cells,and inhibited the activation of MAPK signaling pathway.After injection of D-JNKI1,it promoted apoptosis by activating the apoptosis pathway related factors,and reduced the growth rate and quality of transplanted tumor in nude mice.Conclusion D-JNKI1 can inhibit the proliferation and invasion of hepatocellular carcinoma HepG2 cells and promote their apoptosis by activating apoptotic pathway and reducing the activation of MAPK signaling pathway.
