AEG-1 is associated with hypoxia-induced hepatocellular carcinoma chemoresistance via regulating PI3K/AKT/HIF-1alpha/MDR-1 pathway

Authors

  • Yong Xie Department of Hepatobiliary Surgery, the 2nd XiangYa Hospital of Centre South University, 139#, Renmin Road, Changsha, Hunan, P.R. China
  • De-Wu Zhong Department of Hepatobiliary Surgery, the 2nd XiangYa Hospital of Centre South University, 139#, Renmin Road, Changsha, Hunan, P.R. China

DOI:

https://doi.org/10.17179/excli2016-694

Keywords:

AEG-1, hypoxia, hepatocellular carcinoma, chemoresistance, PI3K/AKT/HIF-1alpha/MDR-1 pathway

Abstract

Hypoxia is a common characteristic of hepatocellular carcinoma (HCC) associated with reduced response to chemotherapy, thus increasing the probability of tumor recurrence. Astrocyte elevated gene-1 (AEG-1) has been involved in a wide array of cancer progression including proliferation, chemoresistance, angiogenesis and metastasis, but its effect on HCC chemoresistance induced by hypoxia is unclear. In this study, expression of AEG-1 and multiple drug resistance (MDR-1) were examined in HCC using immunohistochemical staining and RT-PCR. Furthermore, their expression levels were detected in HCC HepG2 cells in normoxia or hypoxia via RT-PCR and Western blot assays. Specific shRNAs were used to silence AEG-1 expression in HepG2 cells. Results showed AEG-1 and MDR-1 expression were higher in HCC tissues than in adjacent normal tissues. Incubation of HepG2 cells in hypoxia increased expression of AEG-1 and MDR-1, compared to incubation in normoxia. Exposure to hypoxia blunted sensitivity of HepG2 cells to Adriamycin, 5-fluorouracil and cis-platinum, as evidenced by modest alterations in cell viability and apoptosis rate, however the sensitivity was elevated with AEG-1 knockdown. PI3K/AKT/HIF-1/MDR-1 pathway was attenuated following AEG-1 knockdown in hypoxia. Based on these data, it was suggested that AEG-1 is associated with hypoxia-induced hepatocellular carcinoma chemoresistance via regulating PI3K/AKT/HIF-1/MDR-1 pathway. This study uncovered a novel potential target for development of an effective therapy against hypoxia-induced HCC chemoresistance.

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Published

2016-11-30

How to Cite

Xie, Y., & Zhong, D.-W. (2016). AEG-1 is associated with hypoxia-induced hepatocellular carcinoma chemoresistance via regulating PI3K/AKT/HIF-1alpha/MDR-1 pathway. EXCLI Journal, 15, 745–757. https://doi.org/10.17179/excli2016-694

Issue

Vol. 15 (2016)

Section

Original articles

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