Tetrandrine enhances cytotoxicity of cisplatin in human drug-resistant esophageal squamous carcinoma cells by inhibition of multidrug resistance-associated protein 1

Wang,Tian  Hu; Wan,Jing  Yuan; Gong,Xia; Li,Hong  Zhong; Cheng,Yuan

doi:10.3892/or.2012.1999

Tetrandrine enhances cytotoxicity of cisplatin in human drug-resistant esophageal squamous carcinoma cells by inhibition of multidrug resistance-associated protein 1

Authors:
- Tian Hu Wang
- Jing Yuan Wan
- Xia Gong
- Hong Zhong Li
- Yuan Cheng
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Affiliations: Department of Cardiothoracic Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, P.R. China, Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, P.R. China, Department of Neurosurgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, P.R. China
Published online on: August 30, 2012 https://doi.org/10.3892/or.2012.1999
Pages: 1681-1686

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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.

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