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

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