Tumor Biology   2015 年 36 卷 9 期

2015.08.01

Hypoxia-inducible factor-1?± (HIF-1?±) is a major effector in cell survival response to hypoxia, while the roles of HIF-1?± in radiation-induced autophagy are still unclear in breast cancer cells. Human breast cancer carcinoma MCF-7 cells were stably transfected with pSUPER-shRNA against human HIF-1?± or a scrambled sequence with no homology to mammalian genes, named as pSUPER-HIF-1?± and pSUPER-SC, respectively. Cell Counting Kit-8 (CCK-8) assay and colony formation assay were used to detect cell viability, Western blot was used to detect protein expression, monodansylcadaverine (MDC) staining was used to analyze autophagy, and Hoechts/PI staining was used to assess apoptosis. Ionizing radiation (IR) and cobalt chloride (CoCl2) could induce HIF-1?± expression and increase the microtubule-associated protein 1 light chain 3 (MAPLC3)-II/MAPLC3-I ratio, especially in radiation + CoCl2 group. After the silencing of HIF-1?±, the radiosensitivity of MCF-7 cells increased and the autophagy level decreased in response to DNA damage induced by ionizing radiation, but there was no influence on IR-induced apoptosis. HIF-1?± silencing also increased the expression of phospho-Akt, mTOR, and P70S6K and activated the mTOR signals significantly. Hypoxia can induce autophagy and also improve the IR-induced autophagy via the suppression of Akt/mTOR/P70S6K pathway, which consequently lead to radioresistance.