Atelocollagen-delivered siRNA targeting the FABP5 gene as an experimental therapy for prostate cancer in mouse xenografts

Abstract

The gene FABP5 encodes cutaneous fatty acid binding protein (C-FABP) that is up-regulated in prostate cancer where it acts as a putative oncogene. To test the hypothesis that siRNA to FABP5 delivered to the external environment of a prostate cancer would reduce the level of C-FABP in vivo, experiments were established whereby siRNA to FABP5 suspended in atelocollagen was injected around tumour masses produced by PC-3M cells in Balb/c nude mice and compared with the effect of non-specific scrambled siRNA in atelocollagen. At autopsy, the average size of tumours from the groups treated with 10 and 15 mu M siRNA in atelocollagen was significantly (p=0.02) reduced by more than 3-fold, when compared to the controls. In contrast, when compared to the tumours produced by the group treated with scrambled siRNA, treatment with 10 mu M FABP5 siRNA in buffer and 1 or 5 mu M siRNA in atelocollagen did not produce significant differences. Although the dosage of 15 mu M siRNA produced a greater reduction in tumour sizes when compared with 10 mu M, this difference was not significant (p=0.9). Immunohistochemistry and Western blotting revealed that the levels of C-FABP expression in tumours from mice treated with 10 and 15 mu M dosages were lower than those from the other groups. These data demonstrate that FABP5 siRNA delivered by atelocollagen to the external environment surrounding a tumour mass can effectively inhibit prostate cancer cell growth in nude mice when administered in a dose-dependent manner at concentrations of >10 mu M.