Effect of recombinant human endostatin on the radiosensitivity of esophageal carcinoma cells and underlying mechanism

Abstract

Objective To study the effect of recombinant human endostatin (rhES)on the radiosensitivity of esophageal squamous cells KYSE-150 and its preliminary mechanism.Methods Cells were divided into four groups:control group without treatment,rhES group treated with recombinant human endostatin,radiation alone group exposed with X-rays,and combination group exposed with X-rays plus endostatin.Colony formation assay was used to measure cell survival fraction.A single-hit multi-target model was used to fit cell survival curve and calculate the sensitive enhancement ratio (SER).Influence of rhES combined with X-ray radiation on cell cycle and apoptosis was measured by flow cytometry.Expressions of Cyclin B1,Cyclin D1,Bcl-2 and Bax mRNAs were determined by RT-PCR.Protein expressions of HIF-1α,VEGF,and VEGFR were determined by Western blot.Results D0,Dq and SF2 value of KYSE-150 cells decreased along with the concentration of rhES.At D0dose,the SER for 100 and 200 μg/ml rhES was 1.14 and 1.27,respectively.Compared with the radiation alone group,the apoptosis rate and bax expression increased,while the expressions of VEGF and HIF-1α decreased in the combination group (t =7.97,3.02,117.55,7.22,P ＜ 0.05).Conclusions rhES has radiosensitive effect on esophageal carcinoma cells KYSE-150 in vitro by inhibiting the expressions of HIF-1α and VEGF,regulating bax expression,and inducing apoptosis. Key words: Recombinant human endostatin; Esophageal carcinoma cells; Radiosensitivity