title: HIF-1 and NDRG2 contribute to hypoxia-induced radioresistance of cervical cancer Hela cells.
abstract: Hypoxia inducible factor 1 (HIF-1), the key mediator of hypoxia signaling pathways, has been shown involved in hypoxia-induced radioresistance. However, the underlying mechanisms are unclear. The present study demonstrated that both hypoxia and hypoxia mimetic cobalt chloride could increase the radioresistance of human cervical cancer Hela cells. Meanwhile, ectopic expression of HIF-1 could enhance the resistance of Hela cells to radiation, whereas knocking-down of HIF-1 could increase the sensitivity of Hela cells to radiation in the presence of hypoxia. N-Myc downstream-regulated gene 2 (NDRG2), a new HIF-1 target gene identified in our lab, was found to be upregulated by hypoxia and radiation in a HIF-1-dependent manner. Overexpression of NDRG2 resulted in decreased sensitivity of Hela cells to radiation while silencing NDRG2 led to radiosensitization. Moreover, NDRG2 was proved to protect Hela cells from radiation-induced apoptosis and abolish radiation-induced upregulation of Bax. Taken together, these data suggest that both HIF-1 and NDRG2 contribute to hypoxia-induced tumor radioresistance and that NDRG2 acts downstream of HIF-1 to promote radioresistance through suppressing radiation-induced Bax expression. It would be meaningful to further explore the clinical application potential of HIF-1 and NDRG2 blockade as radiosensitizer for tumor therapy.
authors.affiliation: Department of Radiation Medicine, Fourth Military Medical University, Xi'an, China.
authors.forename: Junye
authors.initials: J
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Yongbin
authors.initials: Y
authors.lastname: Chen
authors.forename: Kangchu
authors.initials: K
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Libo
authors.initials: L
authors.lastname: Yao
authors.forename: Guozhen
authors.initials: G
authors.lastname: Guo
mesh_terms: D017209:Apoptosis; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D005260:Female; D006367:HeLa Cells; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism*; D011836:Radiation Tolerance; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000532:radiotherapy
chemical_list: D051793:Hypoxia-Inducible Factor 1; C466228:NDRG2 protein, human; D025521:Tumor Suppressor Proteins