Adenovirus-mediated ING4 expression reduces multidrug resistance of human gastric carcinoma cells in vitro and in vivo

Mao,Zong-Lei; He,Song-Bing; Sheng,Wei-Hua; Dong,Xiao-Qiang; Yang,Ji-Cheng

doi:10.3892/or.2013.2671

Adenovirus-mediated ING4 expression reduces multidrug resistance of human gastric carcinoma cells in vitro and in vivo

Authors:
- Zong-Lei Mao
- Song-Bing He
- Wei-Hua Sheng
- Xiao-Qiang Dong
- Ji-Cheng Yang
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Affiliations: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China, Cell and Molecular Biology Institute, College of Medicine, Soochow University, Suzhou, Jiangsu 215006, P.R. China
Published online on: August 20, 2013 https://doi.org/10.3892/or.2013.2671
Pages: 2187-2194

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Abstract

Chemotherapy is the primary treatment for both resectable and advanced gastric carcinoma, yet multiple drug resistance (MDR) of gastric carcinoma remains a significant therapeutic obstacle. The development of novel strategies to reduce MDR in gastric carcinoma would yield a better outcome following chemotherapy. ING4, a member of the inhibitor of growth (ING) tumor-suppressor family, possesses antitumor and radiosensitization or chemosensitization effects in a variety of human cancers. The present study investigated the effects and possible mechanisms of action of adenovirus-mediated ING4 (AdVING4) on the reversion of human gastric carcinoma cell MDR in vitro and in vivo in nude mouse xenografts. The data showed that the expression of ING4 mRNA and protein was dramatically downregulated (or lost) in gastric carcinoma SGC7901/CDDP cells after CDDP-induced MDR phenotype and in the parental SGC7901 cells. AdVING4‑induced ING4 expression reversed MDR and induced apoptosis of SGC7901/CDDP cells in vitro and in vivo in the SGC7901/CDDP xenograft tumors. Furthermore, AdVING4 substantially downregulated the expression of MDR-related proteins P-gp and MRP1 and apoptosis‑related proteins Bcl-2 and survivin, but upregulated the expression of apoptosis-related protein Bax in the SGC7901/CDDP xenograft tissues. The reversion effects elicited by AdVING4 on gastric cancer cell MDR were closely associated with the downregulation of ATP-binding cassette transporters and activation of apoptotic pathways. Thus, these findings suggest that AdVING4 may be a feasible modulator for the MDR phenotype of gastric carcinoma cells.

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