Authors: | Xie, Yong Zhong, De-Wu |
Title: | AEG-1 is associated with hypoxia-induced hepatocellular carcinoma chemoresistance via regulating PI3K/AKT/HIF-1alpha/MDR-1 pathway |
Language (ISO): | en |
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 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. |
Subject Headings: | AEG-1 hypoxia hepatocellular carcinoma chemoresistance PI3K/AKT/HIF-1-1α/MDR-1 pathway |
URI: | http://hdl.handle.net/2003/35851 http://dx.doi.org/10.17877/DE290R-17875 |
Issue Date: | 2016-11-30 |
Rights link: | https://creativecommons.org/licenses/by/4.0/ |
Appears in Collections: | Original Articles |
Files in This Item:
File | Description | Size | Format | |
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Zhong_30112016_proof.pdf | DNB | 510.63 kB | Adobe PDF | View/Open |
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