Effect And Mechanism On Jagged1Gene Silencing By RNA Interference In Clear Renal Cell Carcinoma Cells

【Objectives】 This study was aimed at investigating the expression of VEGF receptor and Jagged1protein in renal clear cell carcinoma, and researching its clinical significance. We further observe the effects of silencing of Jagged1on cell biology and Akt/mTOR signal pathway in renal carcinoma cell786-0.【Methods】 The expression of VEGFR1，VEGFR2，VEGFR and Jagged1in52cases of renal carcinoma cell (RCC) and its cancer-adjacent and30cases normal tissues were detected by immunohistochemistry. Jagged1-siRNA was transfected to renal carcinoma cell786-0using lipofectamine2000. Detecting Jagged1gene mRNA and protein by RT-PCR and Western Blot. The proliferation and apoptosis of cells will be checked by MTT and TUNEL assay. The expression level of Notch1, Bcl-2, Bax, Pro-caspase3Protein and associated Akt/mTOR signal transduction pathway was checked by Western blot.【Results】 The positive rates of VEGFR1, VEGFR2, VEGFR3and Jagged1was84.62%,86.53%,96.15%,92.30%in RCC, which were higher than that in cancer-adjacent and normal tissues (p <0.05). The high levels of VEGFR and Jagged1protein were correlated to larger tumor size and Fuhrman clasification and TMN stage. The siRNA targeting Jagged1inhibited cell proliferation and induced cell apoptosis, while upregulating Bax and downregulating Bcl-2and procaspase-3. Jagged1siRNA decreased the expression of Notch1and phosphoralated AKT signal transduction pathway.【Conclusion】The expression of VEGFR1, VEGFR2, VEGFR3and Jagged1in RCC is higher and correlate to larger tumor size and Fuhrman clasification and TMN stage, which might pay an important role in pathogenesis in RCC. Silencing Jagged1gene inhibits cell groth and induces cell apoptosis and phosphoralates AKT signal transduction pathway. It migh be considered as a target for anti-tumor therapy。...