2. Academic Validation
  3. Imatinib inhibits the malignancy of hepatocellular carcinoma by suppressing autophagy

Imatinib inhibits the malignancy of hepatocellular carcinoma by suppressing autophagy

  • Eur J Pharmacol. 2021 Sep 5;906:174217. doi: 10.1016/j.ejphar.2021.174217.
Meng-Chao Xiao 1,  Hui Qian 2,  Chen-Kai Huang 3,  Bai-Nan Zheng 4,  Fang-Zhi Yan 4,  Fang Liu 4,  Xin Zhang 4,  Shi-Jie Chen 5,  Cheng Luo 5,  Wei-Fen Xie 6
Affiliations

Affiliations

  • 1 Tongji University School of Medicine, Shanghai, 200120, China.
  • 2 Department of Gastroenterology, Changzheng Hospital, Navy Medical University, Shanghai, 200003, China. Electronic address: qianhui1981@126.com.cn.
  • 3 Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, China.
  • 4 Department of Gastroenterology, Changzheng Hospital, Navy Medical University, Shanghai, 200003, China.
  • 5 Drug Discovery and Design Center, CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), Shanghai, 201203, China.
  • 6 Tongji University School of Medicine, Shanghai, 200120, China; Department of Gastroenterology, Changzheng Hospital, Navy Medical University, Shanghai, 200003, China. Electronic address: weifenxie@medmail.com.cn.
PMID: 34087223 DOI: 10.1016/j.ejphar.2021.174217
Abstract

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.

Keywords

Autophagy; Hepatocarcinoma; Imatinib; Sorafenib; Synergetic effect.

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