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Reversal of multidrug resistance of vincristine‐resistant gastric adenocarcinoma cells through up‐regulation of DARPP‐32

2007; Wiley; Volume: 31; Issue: 9 Linguagem: Inglês

10.1016/j.cellbi.2007.03.020

1095-8355

Liu Hong, Jin Wang, Ying Han, Yunping Zhao, Juan Gao, Jun Wang, Yu Han, Xiaoyin Zhang, Yan Li, Xinmin Zhou, Taidong Qiao, Zhen Chen, Daiming Fan,

Genomics, phytochemicals, and oxidative stress

Here we investigated the roles of DARPP-32 in multidrug resistance (MDR) of gastric cancer cells and the possible underlying mechanisms. We constructed the eukaryotic expression vector of DARPP-32 and transfected it into human vincristine-resistant gastric adenocarcinoma cell line SGC7901/VCR. Up-regulation of DARPP-32 could significantly enhance the sensitivity of SGC7901/VCR cells towards vincristine, adriamycin, 5-fluorouracil and cisplatin, and could decrease the capacity of cells to efflux adriamycin. What's more, the results of subrenal capsule assay confirmed that DARPP-32 might play a certain role in MDR of gastric cancer. DARPP-32 could significantly down-regulate the expression of P-gp and zinc ribbon domain-containing 1 (ZNRD1), but not alter the expression of multidrug resistance-associated protein (MRP) or the glutathione S-transferase (GST). DARPP-32 could also significantly decrease the anti-apoptotic activity of SGC7901/VCR cells. Further study of the biological functions of DARPP-32 might be helpful for understanding the mechanisms of MDR in gastric cancer.