Small interfering RNA (siRNA) provides a promising therapeutic approach in the silencing of disease-causing genes. In the present study, the use of 2'-O-methyl-modified siRNA-cluster of differentiation 31 (siRNACD31), with cationic liposome RNA interference (RNAi)-mate as a carrier, effectively silenced the platelet endothelial cell molecule 1 (PECAM-1) gene of murine hemangioendothelioma cells in vitro. In vivo, 2'-O-methyl-modified siRNACD31 carried by RNAi-mate was successfully delivered, targeting the PECAM-1 gene in the vasculature of nude mouse lung carcinoma xenografts. The growth of the lung carcinoma xenografts was inhibited by the 2'-O-methyl-modified siRNACD31 and RNAi-mate complexes, and the expression of the PECAM-1 protein was downregulated, with a simultaneous decrease in vascular endothelial growth factor (VEGF) protein in the lung carcinoma xenografts. 2'-O-methyl-modified siRNACD31-RNAi-mate complexes may provide a potential therapeutic strategy in lung carcinoma treatment. The effect of PECAM-1 on VEGF expression may possibly be attributed to the function of PECAM-1 signal transduction.
Keywords: carcinoma; platelet endothelial adhesion molecule; small interfering RNA; tumor microenvironment; vascular endothelial growth factor.