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Digestive Diseases and Sciences

, Volume 53, Issue 1, pp 101–107 | Cite as

Reversal of Multidrug Resistance of Adriamycin-resistant Gastric Adenocarcinoma Cells Through the Up-regulation of DARPP-32

  • Liu Hong
  • Yunping  Zhao
  • Jin Wang
  • Ying Han
  • Wei Guo
  • Haifeng Jin
  • Huihong Zhai
  • Feihu Bai
  • Xiaoyin Zhang
  • Taidong Qiao
  • Zhen Chen
  • Daiming FanEmail author
Original Paper

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.

Keywords

DARPP-32 Gastric neoplasm Multidrug resistance P-gp ZNRD1 

Notes

Acknowledgements

This study was supported in part by grants from the Chinese National Foundation of Natural Sciences (30400203)

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Liu Hong
    • 1
  • Yunping  Zhao
    • 1
    • 2
  • Jin Wang
    • 1
  • Ying Han
    • 1
  • Wei Guo
    • 1
    • 2
  • Haifeng Jin
    • 1
  • Huihong Zhai
    • 1
  • Feihu Bai
    • 1
  • Xiaoyin Zhang
    • 1
  • Taidong Qiao
    • 1
  • Zhen Chen
    • 1
  • Daiming Fan
    • 1
    Email author
  1. 1.State Key Laboratory of Cancer Biology & Institute of Digestive DiseasesXijing Hospital, Fourth Military Medical UniversityXi’anChina
  2. 2.Department of Thoracic Surgery, Institute of Surgery ResearchDaping Hospital, Third Military Medical UniversityChongqingChina

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