Effect of silencing 53BP1 gene on radiosensitivity to esophageal cancer ECA109 cell xenograft in nude mice / 中国癌症杂志

ABSTRACT

Background and purpose:p53 binding protein (53BP1) expresses in many normal and tumor cells. In vitroexperiments have conifrmed that inhibition of the protein expression of 53BP1 can effectively eliminate cycle arrest of tumor cells, and increase the radiosensitivity after irradiation. However, thein vivo experiment has not been re-ported. This study aimed to explore the effect of silencing 53BP1 gene on the growth and radiosensitivity to esophageal cancer cell ECA109 xenograft in nude mice.Methods:Forty-eight male BALB/c/nu nude mice were randomly divided into 6 groups ECA109, ECA109/R, ECA109/N, ECA109/NR, ECA109/B and ECA109/BR. Three kinds of prepared cells (ECA109, ECA109/N and ECA109/B) were subcutaneously injected into the paw pads of mice (2×106/100 μL per mouse). The nude mice in ECA109/R, ECA109/NR, and ECA109/BR groups were irradiated with 15 Gy. Tumor growth was monitored every other day on the 6th day after injection. Tumor volume was measured with calipers. Theexpression levels of CHK1, CHK2 and phosphorylated CHK2-T68 protein were examined in different groups by West-ern blot. Apoptotic cell and cell cycle distribution were detected by lfow cytometry assay.Results:Visible tumors were detectable by day 7 after implantation, and the tumor volumes showed no signiifcant differences among all the groups (F=0.67, P=0.69). After irradiation with 15 Gy, tumor volumes in ECA109/BR group were smaller than those in other groups (P=0.03); the growth inhibition rate increased, but the relative growth rate decreased signiifcantly (P=0.01). The q value which relfected the radiosensitizing effect in ECA109/BR group was 1.45. The expressions of CHK1 and CHK2 at protein level in ECA109/BR group were not inlfuenced (P=0.71). However, the level of phosphorylated CHK2-T68 expression decreased signiifcantly after irradiation with 15 Gy (P=0.03). Cell cycle distribution and apoptosis were not signiifcantly different among all the groups (P=0.45).Conclusion:Silencing 53BP1 gene expression could inhibit the growth of esophageal cancer cell xenograft and increase the radiosensitivity to tumors in the nude mice.