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DARPP-32 mediates multidrug resistance of gastric cancer through regulation of P-gp and ZNRD1
Authors:Hong Liu  Wang Jin  Zhao Yunping  Han Zheyi  Zhou Ximin  Guo Wei  Zhang Xiaoyin  Jin Haifeng  Wu Kaichun  Ding Jie  Fan Daiming
Affiliation: a State Key Laboratory of Cancer Biology & Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China
Abstract:Here, we firstly investigated the roles of DARPP-32 in multidrug resistance of gastric cancer cells. Inhibition of DARPP-32 by small interfering RNA led to decreased sensitivity of cells to chemotherapeutic drugs, accompanied by increased capacity of cells to efflux adriamycin. Inhibition of DARPP-32 expression could significantly up-regulate the expression of permeability glycoprotein (P-gp) and zinc ribbon domain-containing 1 (ZNRD1), but not alter the expression of multidrug resistance-associated protein or glutathione stransferase. The DARPP-32 siRNA-mediated MDR could be reversed by inhibitor of P-gp or siRNA of ZNRD1, indicating DARPP-32 might mediate MDR of gastric cancer through regulation of P-gp and ZNRD1.
Keywords:DARPP-32  Multidrug resistance  Gastric neoplasm  ZNRD1  P-gp
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