title: 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.
  
  
  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.
authors.affiliation: Department of Gastroenterology, Taihe Hospital, Hubei Medical University, Shiyan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Qunfang
authors.initials: Q
authors.lastname: Chen
authors.forename: Shu
authors.initials: S
authors.lastname: Jin
authors.forename: Weiping
authors.initials: W
authors.lastname: Deng
authors.forename: Shengbao
authors.initials: S
authors.lastname: Li
authors.forename: Qiang
authors.initials: Q
authors.lastname: Tong
authors.forename: Yuezhou
authors.initials: Y
authors.lastname: Chen
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism* / Q000528:radiation effects; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D003114:Colony-Forming Units Assay; D004351:Drug Resistance / Q000187:drug effects / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000528:radiation effects*; D006801:Humans; D009381:Neoplasms, Radiation-Induced / Q000235:genetics / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011836:Radiation Tolerance; D015854:Up-Regulation; D014700:Verapamil / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D012333:RNA, Messenger; D014700:Verapamil; D017239:Paclitaxel; D002945:Cisplatin