DARPP-32 mediates multidrug resistance of gastric cancer through regulation of P-gp and ZNRD1.
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 transferase. 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.
State Key Laboratory of Cancer Biology & Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
Liu
L
Hong
Jin
J
Wang
Yunping
Y
Zhao
Zheyi
Z
Han
Ximin
X
Zhou
Wei
W
Guo
Xiaoyin
X
Zhang
Haifeng
H
Jin
Kaichun
K
Wu
Jie
J
Ding
Daiming
D
Fan
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology*; D000818:Animals; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000502:physiology*; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000502:physiology*; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D051379:Mice; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014700:Verapamil / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004268:DNA-Binding Proteins; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; C406241:POLR1H protein, human; C497928:PPP1R1B protein, human; D014750:Vincristine; D004317:Doxorubicin; D014700:Verapamil