title: Regulation of radiosensitivity by HDAC inhibitor trichostatin A in the human cervical carcinoma cell line Hela.
abstract: Histone deacetylase (HDAC) inhibitors play an important role in inducing growth arrest, differentiation, and/or apoptosis in cancer cells. Given their ability to disrupt critical biological processes in cancer cells, these agents are emerging as potential therapeutics for cancer. Recently, it has been identified that HDAC inhibitors can also efficiently enhance the radiation sensitivity of cells, both in vitro and in vivo. In this study, we investigated whether the potent HDAC inhibitor, Trichostatin A, modulates the radiation sensitivity of the human cervical carcinoma cell line Hela under hypoxic conditions. We concluded that TSA could significantly inhibit the proliferation of Hela cells in a dose-and time-dependent manner under normoxic and hypoxic conditions. Hypoxia resulted in the cervical carcinoma Hela cells resistant to TSA. The findings from clonogenic survival assays indicate that incubation with TSA for 24 hours prior to irradiation enhances the radiation sensitivity of Hela cells under hypoxic conditions. More generally, we found Hela cells under hypoxic conditions treated with TSA could significantly down-regulate the expressions of HIF-1alpha and VEGF proteins. Taken together, our results demonstrated that TSA acts as a powerful radiosensitizer in Hela cells under hypoxic conditions probably by down-regulated expression of HIF-1alpha and VEGF proteins.
authors.affiliation: Cancer Biology Research Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan, P.R. China. yujj985@yahoo.com
authors.forename: J
authors.initials: J
authors.lastname: Yu
authors.forename: J
authors.initials: J
authors.lastname: Mi
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: A
authors.initials: A
authors.lastname: Wang
authors.forename: X
authors.initials: X
authors.lastname: Tian
mesh_terms: D015687:Cell Hypoxia; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D005260:Female; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000187:drug effects / Q000378:metabolism; D011836:Radiation Tolerance / Q000187:drug effects*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects / Q000378:metabolism
chemical_list: C497442:HIF1A protein, human; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; C012589:trichostatin A