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

Abstract

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.

Retracted:Up-regulation of NOB1 in esophageal squamous cell carcinoma

“…The zinc ribbon domain is a ubiquitous motif in archaeal and eucaryal transcription, and has proven to be a functional domain required for biological activities in TFIIS and TFIIB. [6][7][8][9][10][11] Thus, NOB1 was assumed to be associated with transcription regulation and might play potential roles in mediating some physiologic and pathological functions. Further, the analogous Cys 4 structural motifs were found play important roles in promoting cleavage of the nascent transcript and read-through past the block to elongation.…”

Expression and Prognostic Value of ZNRD1 in Esophageal Squamous Cell Carcinoma

“…The zinc ribbon domain at the C-terminal of ZNRD1 protein, similar to the reported zincribbon motif in human yeast TFIIS [12], was well conserved throughout evolution, including archaea, yeast, drosophila, nematodes, amphibians, and mammals. And the analogous Cys 4 structural motifs were found to occur in many other transcription-associated proteins and to play important roles in promoting cleavage of the nascent transcript and read-through past the block to elongation [13][14][15]. Recently, we have found that ZNRD1 expression was related to multidrug resistance and carcinogenesis of gastric cancer [2].…”

Down-Regulation of miR-27a Might Reverse Multidrug Resistance of Esophageal Squamous Cell Carcinoma

“…MTT assay revealed that miR-27a antagomir cells showed increased sensitivity to both P-gp-related and P-gp-non-related drugs. ADR was used as a probe to evaluate drug accumulation and retention in cancer cells [15]. As the results showed, miR-27a antagomir cells showed increased ADR accumulation and retention and decreased ADR releasing index.…”