Division of Cellular Pathology and Molecular Genetics, School of Cancer Studies, University of Liverpool, 6th Floor, Duncan Building, Daulby Street, Liverpool L69 3GA, UK.
Int J Oncol. 2010 Jan;36(1):69-76.
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 microM 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 microM FABP5 siRNA in buffer and 1 or 5 microM siRNA in atelocollagen did not produce significant differences. Although the dosage of 15 microM siRNA produced a greater reduction in tumour sizes when compared with 10 microM, 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 microM 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 microM.
基因 FABP5 编码皮肤脂肪酸结合蛋白（C-FABP），在前列腺癌中上调，作为潜在的癌基因。为了验证 FABP5 的 siRNA 递送至前列腺癌的外部环境中是否会降低体内 C-FABP 水平的假设，进行了实验，其中 FABP5 的 siRNA 悬浮在去端胶原中，并注射到 Balb/c 裸鼠中由 PC-3M 细胞产生的肿瘤周围，并与去端胶原中的非特异性 scrambled siRNA 的效果进行比较。尸检时，与对照组相比，用 10 和 15 μM siRNA 在去端胶原中处理的组的肿瘤平均大小显著（p=0.02）减少了 3 倍以上。相比之下，与用 scrambled siRNA 处理的组产生的肿瘤相比，用缓冲液中的 10 μM FABP5 siRNA 和 1 或 5 μM siRNA 在去端胶原中处理并未产生显著差异。尽管与 10 μM 相比，15 μM siRNA 的剂量产生了更大的肿瘤体积减少，但这一差异并不显著（p=0.9）。免疫组织化学和 Western blot 显示，用 10 和 15 μM 剂量处理的小鼠肿瘤中的 C-FABP 表达水平低于其他组。这些数据表明，以剂量依赖的方式在浓度>10 μM 时，用去端胶原递送至肿瘤周围外部环境的 FABP5 siRNA 可以有效地抑制裸鼠中的前列腺癌细胞生长。
