By inhibiting PFKFB3, aspirin overcomes sorafenib resistance in hepatocellular carcinoma
By inhibiting PFKFB3, aspirin overcomes sorafenib resistance in hepatocellular carcinoma
复制标题
阿司匹林通过抑制 PFKFB3 克服肝细胞癌中的索拉非尼耐药
DOI：
10.1002/ijc.31022
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发表时间：
2017-12-15
影响因子：
6.4
通讯作者：
Guo, Chuanyong
中科院分区：
文献类型：
--
作者：
Li, Sainan;Dai, Weiqi;Guo, Chuanyong
肝细胞癌（HCC）是发病率和死亡率持续上升的少数几种癌症之一。耐药性是HCC治疗中的主要问题。本研究采用两种索拉非尼耐药肝癌细胞系和裸鼠皮下肿瘤模型，探讨索拉非尼耐药的可能机制，并研究阿司匹林是否能增加肝癌细胞对索拉非尼的敏感性。阿司匹林和索拉非尼的组合在体外和体内均产生针对肝肿瘤的协同抗肿瘤作用。糖酵解和PFKFB 3过表达在索拉非尼耐药中占主导地位，阿司匹林可以靶向和克服。阿司匹林加索拉非尼诱导肿瘤细胞凋亡，而不诱导体重减轻，肝毒性或炎症。我们的研究结果表明，阿司匹林克服索拉非尼耐药，他们的组合可能是一个有效的治疗方法肝癌。
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.