Primary impact of Gli1 on radioresistance in esophageal cancer.

Abstract

Radioresistance is the primary cause for the low efficacy of radiotherapy in the treatment of esophageal cancer (EC). Increasing evidence has demonstrated that the Sonic Hedgehog (Shh) signaling pathway may be involved in the pathology of various tumors, including EC. The present study aimed to examine the association between radioresistance in EC and the Sonic Hedgehog pathway, and to determine whether a downstream transcription factor of the Shh pathway, glioma-associated oncogene family zinc finger 1 (Gli1), serves a primary role in radioresistance. The radiation-resistant cell line Eca109R was established by repeated low dose (cumulative dose 60 Gy) irradiation of the human EC cell line Eca109. The level of cell radiosensitivity was determined by colony formation assay, and the localization of Gli1 was detected using immunofluorescence. Western blotting was used to determine the protein expression levels of Gli1, Shh, patched 1 (Ptch) and smoothened frizzled class receptor (Smo) in the two cell lines. Significantly higher levels of Gli1 were identified in the Eca109R cell line compared with those inEca109 cells (P<0.05). Additionally, western blotting analysis demonstrated an increased expression level of the Gli1, Shh, Ptch and Smo proteins in Eca109R, compared with Eca109 cells (P<0.05). Overexpression of Gli1 in the parental cell line led to decreased levels of radiosensitivity and radiosensitivity of the radioresistant cell line was restored through knockdown of Gli1. The present study demonstrated that Gli1 may be associated with the development of radioresistance in EC.