title: Reversal of multidrug resistance of adriamycin-resistant gastric adenocarcinoma cells through the up-regulation of DARPP-32.
abstract: We have investigated the roles of dopamine and cAMP-regulated phosphoprotein (DARPP-32) in the multidrug resistance (MDR) of gastric cancer cells and the possible underlying mechanisms. The up-regulation of DARPP-32 was found to significantly enhance the sensitivity of cells of human adriamycin (ADR)-resistant gastric adenocarcinoma cell line SGC7901/ADR to vincristine, ADR, 5-fludrouracil and cisplatin. The results of an in vivo drug sensitivity assay confirmed that DARPP-32 may play a specific role in the MDR of gastric cancer. DARPP-32 significantly down-regulated the expression of P-glycoprotein and zinc ribbon domain-containing 1 (ZNRD1), but did not alter the expression of MDR-associated protein or glutathione-S-transferase. The up-regulation of ZNRD1 significantly inhibited the drug sensitivity of gastric cancer cells over-expressing DARPP-32, indicating that ZNRD1 may be important in the DARPP-32-mediated MDR of gastric cancer. DARPP-32 was also able to significantly decrease the anti-apoptotic activity of SGC7901/ADR cells. Further study of the biological functions of DARPP-32 may be helpful for understanding the mechanisms of MDR of gastric cancer cells and developing possible strategies to treat gastric cancer.
authors.affiliation: State Key Laboratory of Cancer Biology & Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Hong
authors.forename: Yunping
authors.initials: Y
authors.lastname: Zhao
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Han
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.forename: Haifeng
authors.initials: H
authors.lastname: Jin
authors.forename: Huihong
authors.initials: H
authors.lastname: Zhai
authors.forename: Feihu
authors.initials: F
authors.lastname: Bai
authors.forename: Xiaoyin
authors.initials: X
authors.lastname: Zhang
authors.forename: Taidong
authors.initials: T
authors.lastname: Qiao
authors.forename: Zhen
authors.initials: Z
authors.lastname: Chen
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000096:biosynthesis / Q000235:genetics*; D018432:Drug Resistance, Multiple / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D012334:RNA, Neoplasm / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; C406241:POLR1H protein, human; C497928:PPP1R1B protein, human; D012334:RNA, Neoplasm