title: Inhibition of Vav3 could reverse the drug resistance of gastric cancer cells by downregulating JNK signaling pathway.
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.
authors.affiliation: Department of General Surgery, the Fourth Affiliated Hospital, Hebei Medical University Shijiazhuang, Shijiazhuang, China.
authors.forename: B
authors.initials: B
authors.lastname: Tan
authors.affiliation: Department of General Surgery, the Fourth Affiliated Hospital, Hebei Medical University Shijiazhuang, Shijiazhuang, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of General Surgery, the Fourth Affiliated Hospital, Hebei Medical University Shijiazhuang, Shijiazhuang, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of General Surgery, the Fourth Affiliated Hospital, Hebei Medical University Shijiazhuang, Shijiazhuang, China.
authors.forename: L
authors.initials: L
authors.lastname: Fan
authors.affiliation: Department of General Surgery, the Fourth Affiliated Hospital, Hebei Medical University Shijiazhuang, Shijiazhuang, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of General Surgery, the Fourth Affiliated Hospital, Hebei Medical University Shijiazhuang, Shijiazhuang, China.
authors.forename: D
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of General Surgery, the Fourth Affiliated Hospital, Hebei Medical University Shijiazhuang, Shijiazhuang, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051567:Proto-Oncogene Proteins c-vav / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D051567:Proto-Oncogene Proteins c-vav; D034741:RNA, Small Interfering; C496621:VAV3 protein, human; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt