Radiosensitivity Enhancement by Arsenic Trioxide in Conjunction with Hyperthermia in the EC-1 Esophageal Carcinoma Cell Line

Abstract


Objective: To explore the effect on radiosensitivity of arsenic trioxide (As203) in conjunction with hyperthermiaon the esophageal carcinoma EC-1 cell line.
Method: Inhibition of EC-1 cell proliferation at differentconcentrations of As203 was assessed using the methyl thiazolyl blue colorimetric method (MTT method),with calculation of IC50 value and choice of 20% of the IC50 as the experimental drug concentration. Blankcontrol, As203, hyperthermia, radiotherapy group, As203 + hyperthermia, As203 + radiotherapy, hyperthermia +radiotherapy and As203 + hyperthermia + radiotherapy groups were established, and the cell survival fraction(SF) was calculated from flat panel colony forming analysis, and fitted by the ‘multitarget click mathematicalmodel’. Flow cytometry (FCM) was used to detect changes in cell apoptosis and the cell cycle.
Results: As203exerted inhibitory effects on proliferation of esophageal carcinoma EC-1 cells, with an IC50of 18.7 μmol/L. Afterjoint therapy of As203 + hyperthermia + radiotherapy, the results of FCM showed that cells could be arrested inthe G2/M phase, and as the ratio of cells in G0/G1 and S phases decreased, cell death became more pronounced.
Conclusion: As203 and hyperthermia exert radiosensitivity effects on esophageal carcinoma EC-1 cells, withsynergy in combination. Mechanistically, As203 and hyperthermia mainly influence the cell cycle distribution ofEC-1 esophageal carcinoma cells, decreasing the repair of sublethal damage and inducing apoptosis, therebyenhancing the killing effects of radioactive rays.

Keywords