20µg of shRNA oligonucleotide were complexed with 2.5µl of in vivo-jetPEI (N/P=6.25) in a total volume of 200µl and injected intratumorally into subcutaneous tumors (CAKI-1 cells) in nude mice. Injections were performed 4 times per week for 4 weeks.

The Delta-like ligand 4 (Dll4) and Notch signaling pathway plays a key role in embryonic vascular development and tumor growth. In this study, we measured the expression of Dll4 in clear cell renal cell carcinoma (ccRCC) and explored the correlation between Dll4 and ccRCC. We used sh-Dll4 treatment in a nude mouse model to observe the effect that inhibition of the Dll4/Notch pathway had on angiogenesis and vasculogenesis. We found up-regulation of Dll4 to be closely correlated with distant metastasis and worse overall survival. Cox regression analysis showed that Dll4 might be a prognostic marker of ccRCC. Blockade of Dll4/Notch signaling inhibited tumor growth in the mouse model via anti-angiogenesis and anti-vasculogenesis effects. We concluded that Dll4 might be a novel therapeutic target for the treatment of ccRCC.