title: Tetrandrine enhances cytotoxicity of cisplatin in human drug-resistant esophageal squamous carcinoma cells by inhibition of multidrug resistance-associated protein 1.
abstract: Multidrug resistance is one of the major causes limiting the efficacy of chemotherapeutic agents to control esophageal cancer. Herein, we investigated that the effect and mechanism of tetrandrine (TET) in the human esophageal squamous carcinoma cisplatin-resistant cell line YES-2/DDP. The human esophageal squamous carcinoma cisplatin-resistant cell line YES-2/DDP was isolated by stepwise selection in increasing concentrations of cisplatin. The CCK-8 method was carried out to measure the cell viability when cells were exposed to TET with or without cisplatin, and the IC50 and resistance index (RI) of cisplatin was then calculated. Real-time RT-PCR and western blotting were used to detect the mRNA and protein expression of multidrug resistance 1 (MDR1), multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP), respectively. Flow cytometry was adopted to determine CMFDA efflux and cell apoptosis, respectively. The resulting cell line YES-2/DDP was 16.4-fold resistant to cisplatin, the cytotoxicity of cisplatin to YES-2/DDP cells was enhanced by TET in a dose-dependent manner. Further, it was found that the expression of MDR1 and BCRP was similar in different treated cells. In contrast, the expression of MRP1 was markedly increased in YES-2/DDP cells, which was dose-dependently decreased by TET. In agreement with the results, MRP1 activity was also reversed by TET. In conclusion, TET possesses a reversal effect on drug resistance in YES-2/DDP cells through downregulation of MRP1, and has the potential to be an adjunct to chemotherapy for esophageal cancer.
authors.affiliation: Department of Cardiothoracic Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, PR China.
authors.forename: Tian Hu
authors.initials: TH
authors.lastname: Wang
authors.forename: Jing Yuan
authors.initials: JY
authors.lastname: Wan
authors.forename: Xia
authors.initials: X
authors.lastname: Gong
authors.forename: Hong Zhong
authors.initials: HZ
authors.lastname: Li
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cheng
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D044182:Benzylisoquinolines / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D044182:Benzylisoquinolines; D002945:Cisplatin; D004365:Drugs, Chinese Herbal; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C513055:ABCB1 protein, human; C116614:ABCG2 protein, human; C009438:tetrandrine; C421109:multidrug resistance-associated protein 1