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Inhibition of Vav3 could reverse the drug resistance of gastric cancer cells by downregulating JNK signaling pathway

Cancer Gene Therapy volume 21, pages 526–531 (2014)Cite this article

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Abstract

This study aims to investigate the effect and mechanism of Vav3 on the multidrug resistance of gastric cancer. Fluorescence quantitative RT-PCR and western blot assay were used to detect Vav3 and drug resistance genes in gastric cancer tissues as well as gastric cell lines such as SGC7901, SGC7901/adriamycin (ADR) and GES-1. Besides, Vav3-specific small interfering RNA (Vav3-siRNA) was applied to inhibit Vav3 in SGC7901/ADR, and SRB assay was used to determine chemosensitivity. After that, drug resistance genes and proteins in MAPK and PI3K/AKT signaling pathway were detected after Vav3-siRNA transfection. The results showed that overexpressed Vav3 was found in gastric cancer tissues and SGC7901 and SGC7901/ADR cells. Activity of SGC7901/ADR cells transfected with Vav3-siRNA combined with 5-fluorouracil/oxaliplatin was much lower than that of control groups, and MDR1/P-gp, GST-π and Bcl-2, Bax genes were significantly downregulated in Vav3-siRNA transfection group. AKT, ERK and p38 total protein and their phosphorylation levels showed no significant change in Vav3-siRNA-transfected SGC7901/ADR cells, whereas the ratio of C-Jun phosphorylation levels to total C-Jun protein was significantly downregulated. The results suggested that Vav3 may play a role in drug resistance of gastric cancer by inhibiting drug resistance genes MDR1/P-gp, GST-π and Bcl-2 through regulating the JNK signaling pathway.

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Authors and Affiliations

  1. Department of General Surgery, the Fourth Affiliated Hospital, Hebei Medical University Shijiazhuang, Shijiazhuang, China

    B Tan, Y Li, Q Zhao, L Fan, Y Liu, D Wang & X Zhao

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  1. B Tan
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Correspondence to Y Li.

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Tan, B., Li, Y., Zhao, Q. et al. Inhibition of Vav3 could reverse the drug resistance of gastric cancer cells by downregulating JNK signaling pathway. Cancer Gene Ther 21, 526–531 (2014). https://doi.org/10.1038/cgt.2014.59

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  • DOI: https://doi.org/10.1038/cgt.2014.59

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