Up-regulation of P-glycoprotein is involved in the increased paclitaxel resistance in human esophageal cancer radioresistant cells

Abstract

Objective. Development of drug and radiation resistance is one of the major causes of cancer treatment failure with chemoradiotherapy. Whether radiotherapy affects drugs resistance in esophageal cancer cells remain to be determined. The purpose of the study was to investigate the change of drug-sensitivity and P-glycoprotein (P-gp) expression in ionization radiation-induced human esophageal cancer radioresistant cells. Materials and methods. Radioresistant cells were established by means of continuous fractionated gamma-ray irradiation on human esophageal squamous cancer cell line EC9706. The radiosensitivity and drug-sensitivity between established radioresistant cells and parental cells were detected by a colony-forming assay and 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, respectively. The expressions of multidrug resistance type 1 gene (MDR1) mRNA and protein for P-gp were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot methods. The roles of P-gp activity in irradiation-induced drugs resistance were studied by using verapamil, an inhibitor of P-gp activity. Results. The esophageal cancer radioresistant cells showed an increased cisplatin or paclitaxel resistance. Compared with their parental cells, the expressions of MDR1 mRNA and protein for P-gp were increased significantly in radioresistant cells. Verapamil reduced paclitaxel resistance but had no effect on cisplatin resistance in human esophageal cancer radioresistant cells. Conclusions. These results suggested that up-regulation of P-gp is involved in the increased paclitaxel resistance but not cisplatin resistance in ionization radiation-induced human esophageal squamous cancer radioresistant cells.