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: Liu Hong, Yunping Zhao, Jin Wang, Ying Han, Wei Guo, Haifeng Jin, Huihong Zhai, Feihu Bai, Xiaoyin Zhang, Taidong Qiao, Zhen Chen, Daiming Fan
• Journal: Digestive diseases and sciences (Dig Dis Sci) Vol. 53 Issue 1 Pg. 101-7 (Jan 2008) ISSN: 0163-2116 [Print] United States
• PMID: 17492506 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Biomarkers, Tumor
• DNA-Binding Proteins
• Dopamine and cAMP-Regulated Phosphoprotein 32
• POLR1H protein, human
• PPP1R1B protein, human
• RNA, Neoplasm

Topics

• Adenocarcinoma (drug therapy, genetics, pathology)
• Antineoplastic Agents (therapeutic use)
• Apoptosis
• Biomarkers, Tumor
• Blotting, Western
• Cell Line, Tumor
• DNA-Binding Proteins (biosynthesis, genetics)
• Dopamine and cAMP-Regulated Phosphoprotein 32 (biosynthesis, genetics)
• Drug Resistance, Multiple (genetics)
• Gene Expression Regulation, Neoplastic
• Humans
• RNA, Neoplasm (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Stomach Neoplasms (drug therapy, genetics, pathology)
• Up-Regulation