Synergic effects of the combination of VEGF-targeted shRNA and Taxol on human prostate cancer DU145 both in vitro and in vivo

In this study, the antitumor activities of VEGF shRNA and tubulin inhibitors on human prostate cancer DU145 cells was investigated, and shRNA transient expression plasmid pCSH1-VEGF targeting VEGF mRNA was constructed.  The silence efficiency of pCSH1-VEGF was detected by RT-PCR assay, Western  blotting, and Matrigel invasion assay.  The sensitivity change of DU145 cells to Taxol and vincristine (VCR) was measured by MTT assay.  To detect the effects of pCSH1-VEGF and Taxol in vivo, nude mice model of DU145 xenograft tumor was established by subcutaneous inoculation.  The results showed that transcription  and expression of VEGF were knocked by pCSH1-VEGF in DU145 cells.  Matrigel invasion assay results showed that pCSH1-VEGF significantly reduced the migration of DU145 cells with inhibitory rate of 56.1%.  Furthermore, pCSH1-VEGF enhanced the sensitivity of DU145 cells to Taxol and vincristine, and the values of IC₅₀  decreased by 77.3% and 92.6%, respectively.  In vivo experiment showed that Taxol, pCSH1-VEGF, combination of pCSH1-VEGF and Taxol inhibited tumor growth by the rates of 48.8%, 56.2% and 81.8%,    respectively.  The coefficient of drug interaction (CDI) of pCSH1-VEGF and Taxol was 0.82.  The data   suggested that VEGF shRNA could significantly enhance the sensitivity of human prostate cancer to tubulin  inhibitors.