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By inhibiting PFKFB3, aspirin overcomes sorafenib resistance in hepatocellular carcinoma
Author(s) -
Li Sainan,
Dai Weiqi,
Mo Wenhui,
Li Jingjing,
Feng Jiao,
Wu Liwei,
Liu Tong,
Yu Qiang,
Xu Shizan,
Wang Wenwen,
Lu Xiya,
Zhang Qinghui,
Chen Kan,
Xia Yujing,
Lu Jie,
Zhou Yingqun,
Fan Xiaoming,
Xu Ling,
Guo Chuanyong
Publication year - 2017
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.31022
Subject(s) - sorafenib , hepatocellular carcinoma , aspirin , medicine , in vivo , apoptosis , pharmacology , cancer research , drug resistance , oncology , biology , biochemistry , microbiology and biotechnology
Hepatocellular carcinoma (HCC) is one of the few cancers with a continuous increase in incidence and mortality. Drug resistance is a major problem in the treatment of HCC. In this study, two sorafenib‐resistant HCC cell lines and a nude mouse subcutaneously tumor model were used to explore the possible mechanisms leading to sorafenib resistance, and to investigate whether aspirin could increase the sensitivity of hepatoma cells to sorafenib. The combination of aspirin and sorafenib resulted in a synergistic antitumor effect against liver tumors both in vitro and in vivo . High glycolysis and PFKFB3 overexpression occupied a dominant position in sorafenib resistance, and can be targeted and overcome by aspirin. Aspirin plus sorafenib induced apoptosis in tumors without inducing weight loss, hepatotoxicity or inflammation. Our results suggest that aspirin overcomes sorafenib resistance and their combination may be an effective treatment approach for HCC.