Jing S.,Hebei Medical University |
Wang Y.,Military General Hospital of Beijing Military Region |
Wang J.,Hebei Medical University |
Sun G.,Hebei University |
And 3 more authors.
Chinese Journal of Cancer Biotherapy | Year: 2015
Objective: To investigate the effect of arsenic trioxide (As2O3) on proliferation, cycle progression, apoptosis and radio-sensitivity of esophageal carcinoma cells under hypoxia. Methods: Human esophageal carcinoma Eca109 cells were treated with different concentrations of As2O3 or doses of radiation under a hypoxic condition mimicked cobalt chloride (CoCl2). At different time points after treatment, cell viability was determined by MTT assay, cell cycle progression and apoptosis by flow cytometry (FCM), and expression of HIF-1α and p27 at the protein level by Western blotting. Results: In time- and dose-dependent manners, As2O3 inhibited Eca109 cell proliferation similarly under both normoxic and hypoxic conditions (P>0.05). However, radiation-mediated inhibition of Eca109 cell proliferation was significantly less strong under hypoxia than under normoxia (P<0.05). Compared with normoxia, hypoxia increased cell cycle arrest at the G0/G1 phase and decreased the proportion of cells at the G2/M phase (P<0.05). As2O3 induced cell cycle arrest at the G2/M phase and reduced the proportion of cells at the G0/G1 phase under hypoxia. The combination of As2O3 and irradiation resulted in more significant apoptosis in Eca109 cells as compared with the use of As2O3 and irradiation each alone (P<0.05). Under hypoxia, HIF-1α and p27 protein contents were significantly increased as compared with normoxia (P<0.05), but the increase was significantly attenuated by As2O3 (P<0.05). Conclusions: Under hypoxia, As2O3 may increase the sensitivity esophageal carcinoma cells to radiation, possibly through down-regulating the expression of HIF-1α and its down-stream target p27, thus releasing G0/G1 phase arrest and inducing G2/M phase arrest. © 2015, Editorial office of Chinese Journal of Cancer Biotherapy. All rights reserved.