Xie, YongZhong, De-Wu2017-03-132017-03-132016-11-301611-2156http://hdl.handle.net/2003/3585110.17877/DE290R-17875Hypoxia 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 metas- tasis, 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 evi- denced 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 tar- get for development of an effective therapy against hypoxia-induced HCC chemoresistance.enEXCLI Journal;Vol. 15, 2016https://creativecommons.org/licenses/by/4.0/AEG-1hypoxiahepatocellular carcinomachemoresistancePI3K/AKT/HIF-1-1α/MDR-1 pathway61010.17179/excli2016-694article (journal)