title: Hypoxia-Inducible Factor 1-Alpha Regulates Cancer-Inhibitory Effect of Human Mesenchymal Stem Cells.
abstract: Mesenchymal stem cells (MSCs) have been shown to be able to inhibit cancer cells growth. In this study, we investigate the role and the molecular mechanism of hypoxia-inducible factor 1-alpha (HIF-1α) in inhibition of cancer cell proliferation by human MSCs through depletion and overexpression of HIF-1α in human MSCs. We found that the cell culture medium from HIF-1α-depleted Z3 cells significantly promotes breast cancer MCF-7 cell proliferation and colony formation. The expression of p21 is increased in MCF-7 cells, but p53 level remains unchanged. In contrast, the cultured medium from HIF-1α-overexpressed Z3 cells dramatically inhibits MCF-7 cell proliferation and colony formation. The expression of p21 is inhibited in MCF-7 cells, but p53 does not change. We conclude HIF-1α promotes inhibitory effect of human MCSs on breast cancer cell proliferation and colony formation. This process is tightly correlated with cell cycle protein p21 level in cancer cells.
authors.affiliation: Institute of Orthopedics, The First Affiliated Hospital of Chinese PLA General Hospital, 51 Fucheng Road, Haidian District, Beijing, 100048, China. yuanh1998@163.com.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Chinese PLA General Hospital, 51 Fucheng Road, Haidian District, Beijing, 100048, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Bai
authors.affiliation: Institute of Orthopedics, The First Affiliated Hospital of Chinese PLA General Hospital, 51 Fucheng Road, Haidian District, Beijing, 100048, China.
authors.forename: Shu-Xun
authors.initials: SX
authors.lastname: Hou
authors.affiliation: Institute of Orthopedics, The First Affiliated Hospital of Chinese PLA General Hospital, 51 Fucheng Road, Haidian District, Beijing, 100048, China.
authors.forename: Jin-Shu
authors.initials: JS
authors.lastname: Tang
authors.affiliation: Institute of Orthopedics, The First Affiliated Hospital of Chinese PLA General Hospital, 51 Fucheng Road, Haidian District, Beijing, 100048, China.
authors.forename: Xiu-Xiu
authors.initials: XX
authors.lastname: Shi
authors.affiliation: Institute of Orthopedics, The First Affiliated Hospital of Chinese PLA General Hospital, 51 Fucheng Road, Haidian District, Beijing, 100048, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Qin
authors.affiliation: Institute of Orthopedics, The First Affiliated Hospital of Chinese PLA General Hospital, 51 Fucheng Road, Haidian District, Beijing, 100048, China.
authors.forename: Neng
authors.initials: N
authors.lastname: Ren
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D015687:Cell Hypoxia; D049109:Cell Proliferation; D003470:Culture Media / Q000737:chemistry; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D061986:MCF-7 Cells; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D033581:Stem Cell Transplantation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C493956:CDKN1A protein, human; D003470:Culture Media; D050759:Cyclin-Dependent Kinase Inhibitor p21; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: HIF-1α; MCF-7; MSCs; p21; p53