期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 906, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ejphar.2021.174217
关键词
Imatinib; Autophagy; Hepatocarcinoma; Sorafenib; Synergetic effect
资金
- National Natural Science Foundation of China [82030021, 82072641]
- Shanghai Science and Technology Foundation [201740145]
The study demonstrated the inhibitory effect of imatinib on HCC cells and xenografts, possibly through suppressing the autophagic pathway. Additionally, combined treatment of imatinib and sorafenib showed a synergistic effect in HCC cells.
Hepatocellular carcinoma (HCC) is one of the most common cancers and is associated with high morbidity and mortality rates. Recent research indicated that imatinib, a selective tyrosine kinase inhibitor, suppressed the growth of hepatocellular carcinoma. However, the effect of imatinib on HCC and its mechanism remain under investigated. In this study, we demonstrated that imatinib inhibited the proliferation, migration and invasion of HCC cells in vitro and exerted antitumour effects on HCC xenografts in mice in vivo. Imatinib treatment decreased the phosphorylation of AKT and increased the levels of both p62 (protein sequestosome 1) and LC3 (microtubule-associated protein 1A/1B-light chain 3) in HCC cells and HCC xenografts. Scanning confocal microscopy analysis with a mRFP-GFP-LC3 reporter and transmission electron microscopy analysis revealed that imatinib suppressed the autophagic flux by obstructing the formation of autolysosomes. Moreover, imatinib reversed the autophagy induced by sorafenib, and combined treatment with imatinib and sorafenib exerted a synergetic effect in HCC cells compared with monotherapy. Our collective data suggested that imatinib may target HCC by acting as an inhibitor of both tyrosine kinase and autophagy; here, we propose that imatinib could be a promising therapeutic agent for HCC in the clinic.
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