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FXYD5 promotes sorafenib resistance through the Akt/mTOR signaling pathway in hepatocellular carcinoma

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机构： [1]The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China [2]The First Hospital of Hunan University of Chinese Medicine, Changsha, China [3]College of Life Science and Technology, Jinan University, Guangzhou, China [4]Department of Breast Disease, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China [5]The Biomedical Translational Research Institute, Jinan University, Guangzhou, China

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关键词： HCC Sorafenib resistance FXYD5 Akt mTOR signaling pathway

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Tumor chemoresistance is often a major cause for the failure of chemotherapy. The resistance of hepatocellular carcinoma (HCC) cells to sorafenib significantly limits its therapeutic effect in HCC patients. For the first time, we found that FXYD domain-containing ion transport regulator 5 (FXYD5) is highly expressed in sorafenib-resistant HCC cells. In addition, the protein expression level of FXYD5 was markedly higher in HCC tissues than in par-acancerous tissues. Remarkably, downregulation of FXYD5 expression in Huh7/sora cells reversed their resis-tance to sorafenib. Moreover, overexpression of FXYD5 reduced the sensitivity of HCC cells to sorafenib, while the downregulation of its expression in HCC cells had the opposite effect. We also found abnormal activation of the Akt/mTOR signaling pathway in Huh7/sora cells. Furthermore, MK2206, an Akt inhibitor, was found to significantly increase the sensitivity of HCC cells to sorafenib. More importantly, the expression level of p-Akt was positively correlated with the expression of FXYD5 in HCC tissues. Therefore, mechanistically, FXYD5 en-hances the resistance of HCC cells to sorafenib by activating the Akt/mTOR signaling pathway. In conclusion, this study showed that the activation of the FXYD5/Akt/mTOR signaling axis plays key role in the resistance of HCC cells to sorafenib, and FXYD5 may represent a new potential target for HCC therapy.

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出版当年[2021]版：

大类 | 3 区医学

小类 | 3 区药学

最新[2025]版：

大类 | 3 区医学

小类 | 2 区药学

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出版当年[2020]版：

Q2 PHARMACOLOGY & PHARMACY

最新[2023]版：

Q1 PHARMACOLOGY & PHARMACY

影响因子： 4.2 最新[2023版] 4.3 最新五年平均 4.432 出版当年[2020版] 4.014 出版当年五年平均 3.263 出版前一年[2019版] 5.195 出版后一年[2021版]

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第一作者机构： [1]The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China

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