Atelocollagen-delivered siRNA targeting the FABP5 gene as an experimental therapy for prostate cancer in mouse xenografts.
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.
Forootan
Shiva S
SS
Division of Cellular Pathology and Molecular Genetics, School of Cancer Studies, University of Liverpool, 6th Floor, Duncan Building, Daulby Street, Liverpool L69 3GA, UK.
Bao
Zheng Z
ZZ
Forootan
Farzad S
FS
Kamalian
Laleh
L
Zhang
Yu
Y
Bee
Alix
A
Foster
Christopher S
CS
Ke
Youqiang
Y
D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D003094:Collagen / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism*; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism*; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism*
C082667:Fabp5 protein, mouse; D050556:Fatty Acid-Binding Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; C059821:atelocollagen; D003094:Collagen