By inhibiting PFKFB3, aspirin overcomes sorafenib resistance in hepatocellular carcinoma.

Abstract:

: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.

journal_name

Int J Cancer

authors

Li S,Dai W,Mo W,Li J,Feng J,Wu L,Liu T,Yu Q,Xu S,Wang W,Lu X,Zhang Q,Chen K,Xia Y,Lu J,Zhou Y,Fan X,Xu L,Guo C

doi

10.1002/ijc.31022

subject

Has Abstract

pub_date

2017-12-15 00:00:00

pages

2571-2584

issue

12

eissn

0020-7136

issn

1097-0215

journal_volume

141

pub_type

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