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1. Scand J Gastroenterol. 2012 May 1. [Epub ahead of print]

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

Wang Y, Chen Q, Jin S, Deng W, Li S, Tong Q, Chen Y.

Department of Gastroenterology, Taihe Hospital, Hubei Medical University , Shiyan
, China.

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.

PMID: 22545578 [PubMed - as supplied by publisher]