title: The role of hypoxia-inducible factor-1α in radiation-induced autophagic cell death in breast cancer cells.
abstract: Hypoxia-inducible factor-1α (HIF-1α) is a major effector in cell survival response to hypoxia, while the roles of HIF-1α 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-1α or a scrambled sequence with no homology to mammalian genes, named as pSUPER-HIF-1α 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-1α 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-1α, 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-1α 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.
authors: Key Laboratory of Radiobiology (Ministry of Health), School of Public Health, Jilin University, Changchun, 130021, China.
authors: Rui
authors: R
authors: Zhong
authors: Department of Ultrasound, The 1st Hospitals Affiliated to Jilin University, Changchun, 130021, China.
authors: Huiying
authors: H
authors: Xu
authors: Department of Stomatology, The 1st Hospitals Affiliated to Jilin University, Changchun, 130021, China.
authors: Ge
authors: G
authors: Chen
authors: Key Laboratory of Radiobiology (Ministry of Health), School of Public Health, Jilin University, Changchun, 130021, China.
authors: Gang
authors: G
authors: Zhao
authors: Department of Radiation Oncology, The 1st Hospitals Affiliated to Jilin University, Changchun, 130021, China.
authors: Yan
authors: Y
authors: Gao
authors: Key Laboratory of Radiobiology (Ministry of Health), School of Public Health, Jilin University, Changchun, 130021, China.|Department of Radiation Oncology, The 1st Hospitals Affiliated to Jilin University, Changchun, 130021, China.
authors: Xiaodong
authors: X
authors: Liu
authors: Key Laboratory of Radiobiology (Ministry of Health), School of Public Health, Jilin University, Changchun, 130021, China. shmm2001@126.com.|Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, R3T 3T2, Canada. shmm2001@126.com.
authors: Shumei
authors: S
authors: Ma
authors: Department of Radiation Oncology, The 1st Hospitals Affiliated to Jilin University, Changchun, 130021, China. zrcc111@126.com.
authors: Lihua
authors: L
authors: Dong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001343:Autophagy / Q000235:genetics* / Q000528:radiation effects; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D015687:Cell Hypoxia / Q000235:genetics / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D004249:DNA Damage / Q000528:radiation effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D061986:MCF-7 Cells; D051379:Mice; D009381:Neoplasms, Radiation-Induced / Q000235:genetics* / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics; D011839:Radiation, Ionizing
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D034741:RNA, Small Interfering
keywords: Apoptosis; Autophagy; Breast cancer; HIF-1α; Radiosensitivity