Regulatory effect of autophagy on the resistance of human liver cancer cell Huh7 to lenvatinib
- VernacularTitle:自噬在人肝癌细胞Huh7对仑伐替尼耐药中的调节作用
- Author:
Dahong CHEN
1
;
Yafei WU
1
;
Wenjing DIAO
1
;
Huihua YANG
1
;
Pengjuan MAO
1
;
Qin LI
1
Author Information
1. Dept. of Clinical Pharmacy,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200080,China
- Publication Type:Journal Article
- Keywords:
autophagy;
lenvatinib;
liver cancer cell;
drug resistance
- From:
China Pharmacy
2024;35(8):961-966
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the regulatory effect of autophagy on the resistance of human liver cancer cell Huh7 to lenvatinib. METHODS Using human liver cancer cell Huh7 as subject, the lenvatinib-resist cell model (Huh7-LR) was generated by the low-dose gradient method combined with long-term administration. The sensitivity of parental cell Huh7 and drug-resistant cell Huh7-LR to lenvatinib was detected by using CCK-8 assay and flow cytometry. Western blot assay and GFP-mCherry-LC3 plasmid transfection were performed to detect the expression levels of autophagic protein Beclin-1, autophagic adapter protein sequestosome 1 (p62), microtubule-associated protein 1 light chain 3 (LC3) and autophagic level. Furthermore, an autophagy activation model was constructed by cell starvation, the protein expression of p62 and autophagy level were detected by using Western blot assay and GFP-mCherry-LC3 plasmid transfection, and the effect of autophagy activation on the sensitivity of Huh7-LR cells to lenvatinib was detected by flow cytometry. RESULTS Compared with parental cells, the drug resistance index of Huh7-LR cells was 6.2; protein expression of p62 was increased significantly, while apoptotic rate, protein expression of Beclin-1 and LC3Ⅱ/ LC3Ⅰ ratio were all reduced significantly (P<0.05 or P<0.01); the level of autophagy was decreased to some extent. Autophagy activation could significantly increase the protein expression of p62 in Huh7-LR cells (P<0.05) and autophagy level, and significantly increase its apoptotic rate (P<0.05). CONCLUSIONS Autophagy is involved in lenvatinib resistance, and activating autophagy can reverse the resistance of liver cancer cells to lenvatinib to some extent.