Effects Of Silencing VCAM-1 Gene By RNA Interference Carried By Lentiviral Vectoron The Human Tongue Squamous Cell Carcinoma Xenografts In Nude Mice

Objective:To investigate the inhibition effect of vascular cell adhesion molecule-1 (VCAM-1) gene silencing on transplanted tumor growth by injecting lentiviral vector carrying VCAM-1-shRNA into the tumor tissue.Methods:The Tca-8113 cells were injected into BALB/c nude mice to form subcutaneous squamous cell carcinoma model. The diameter of xenografts was about 2.5mm after one week, the 18 mice were randomly divided into three groups according to tumor size:the interference group; the negative control group; the blank control group. Different interventions were given for different groups:the interference group:VCAM-1-shRNA lentiviral particles were injected into tumors(5×106TU,0.1 mL); the negative control group:non-transfected lentivirus vectors were injected into tumor (5×106TU,0.1mL); the blank control group:NS were injected into tumor (0.1mL). Once every three days and consecutive seven injections. Nextly, we have observed the tumors growth in nude mice, measured the long and short diameter of the xenografts, calculated the volume of xenografts and transplated tumor growth curve. At last, the mice were killed after four weeks, we removed the transplanted tumors, measured the tumors'weight and calculated the inhibition rate. We observed the morphological features of the transplanted tumors by hematoxylin-eosin staining(HE) morphology and used immune-histochemistry technology to detect VCAM-1 protein expression and microvessel density (MVD) changes of tumor tissues marked with CD31 in each group. Subsquently, we performed image analysis system to measure the average optical density(OD) of VCAM-1 protein expression values, and analyzed the correlation between the OD values and MVD values.Results:1.Three groups of nude mice transplantation tumor tissues were squamous cell carcinoma confirmed by pathological examination.2.The growth of transplanted tumors in the interference group was markedly lower than those of the other two groups,at the same time the volume was smaller and the weight was lighter, the difference was statistically significant,P<0.05,the tumor weight inhibition rate was 36.21%.3.The values of OD and MVD in the interference group were significantly reduced compared with the other groups, and the difference was statistically significant, P<0.05.4.The value of OD of the VCAM-1 protein expression and the value of MVD were positively correlated(r=0.834,P<0.05).Conclusions:The lentivirus-delivered VCAM-1-shRNA can inhibit the proliferation and tumor angiogenesis of transplantation tumor of human tongue squamous cell carcinoma effectively, it also can effectively interfere the expression of VCAM-1 protein, these results suggest that VCAM-1 could be a potent target for gene therapy of oral squamous cell carcinoma.