Effects Of RNA Interference Targeting Vascular Endothelial Growth Factor On Xenografts Of Drug-Resistant Tongue Cancer Cells

Objective: To study the interference effects of short hairpin RNA (shRNA) targeting vascular endothelial growth factor on xenografts of drug-resistant tongue cancer cells, as well as the possible mechanisms.Methods: Drug-resistant tongue caner cells Tca/DDP were injected subcutaneously into the nude mice in the right underside backs to establish xenograft models, and randomly divided into non-transfected group, mock control group, control group transfected with scrambled sequence plasmid, interference group transfected with VEGF-shRNA expression plasmid, with 6 mice in each group. Since the 7^th day after subcutaneous injection, liposome-mediated plasmid transfection was done in the latter 3 group every 3 days; xenografts were observed and tumor growth curve was measured. After the 10^th transfection, tumors were detached for weighing. Then in situ hybridization assay was chosen to test VEGF mRNA, Western blotting to test VEGF protein. Finally, immunohistochemical staining was applied to detect CD34 and Ki67 for investigating the microvessel parameters and cell proliferation, as well as P-gp, bcl-2 and ERK2 protein.Results: Tumor growth in VEGF-shRNA interference group was significantly slow. Tumor weight, microvessel parameters, cell proliferation, VEGF mRNA, and expression of VEGF, P-gp, bcl-2 as well as ERK2 protein were less than in the other 3 groups, respectively (P<0.05).Conclusions: RNA interference targeting VEGF can inhibit the growth, proliferation, angiogenesis and P-gp expression of the xenografts of drug-resistant tongue cancer cells through decreasing the expression of bcl-2 and ERK2, suggesting that it may become a potential therapy for drug-resistant tongue squamous cell cancer.