Objective  This study aims to investigate the effects of 17-allylamino-17-desmethoxy-geldanamycin(17-AAG) on the gene and protein expressions of VEGF and STAT3 pathways in MKN-45 human gastric cancer cells, and explore the potential mechanisms of the STAT3 signaling pathway that mediate these effects.

  Methods  MKN-45 cells were seeded in Dulbecco's Modified Eagle Medium.The thiazolyl blue method, i.e., methyl thiazolyl tetrazolium assay, was performed to evaluate the inhibitory effects of 17-AAG on the proliferation of MKN-45 cells at different times, with different doses.The gene and protein expression of VEGF and STAT3 were determined by reverse transcription polymerase chain reaction(RT–PCR) and Western blot analysis.

  Results  MKN-45 cells were treated with 17-AAG at 0.165 mg/L to 10 mg/L for 24 and 48 h, respectively.17-AAG significantly inhibited MKN-45 cell proliferation in a time-and dose-dependent manner.The results of the RT–PCR and Western blot assays showed that the gene and protein expressions of VEGF and STAT3 in MKN-45 cells induced by 17-AAG were significantly down-regulated in a dose-dependent manner when the cells were treated with 17-AAG at 1.0, 2.0, 3.0, and 5.0 mg/L for 48 h.The gene and protein expressions of VEGF and STAT3 in the MKN-45 cells were significantly down-regulated in a time-dependent manner when the cells were treated with 17-AAG at 3.0 mg/L for 12, 24, and 48 h.

  Conclusion  The drug 17-AAG can inhibit cell proliferation and down-regulate the gene and protein expressions of VEGF and STAT3 in MKN-45 human gastric cancer cells in vitro; the down-regulation of VEGF expression may be associated with the STAT3 signaling pathway.