Small interfering RNA targeting Raf-1 inhibits tumor growth in vitro and in vivo.
Raf-1 is a cytosolic serine-threonine kinase that plays an important role in tumor cell growth, proliferation, and apoptosis. Upregulated Raf-1 activity has also been implicated in tumor angiogenesis and metastasis. In this study, we used a promising new RNA interfering technology that targets Raf-1 mRNA both in vitro and in vivo. We initially found that Raf-1 siRNA markedly reduced Raf-1 mRNA in MDA-MB-435 cells in vitro by approximately 75% compared to control siRNA treatment groups. Raf-1 siRNA also reduced cell number by inducing apoptosis in a number of cell lines including HUVEC, MDA-MB-435, and C6 cells. After screening several histidine-lysine polymers in complex with Raf-1 siRNA to reduce tumor growth, we further evaluated the efficacy of this siRNA in complex with the optimal histidine-lysine carrier to reduce the tumor growth in vivo. MDA-MB-435 xenografts treated by intratumoral injections of Raf-1 siRNA were significantly reduced compared with the control groups. By the fourth measurement, tumor growth was reduced by nearly 60% in the Raf-1 siRNA treatment group compared with the untreated group (P < .02). Taken together, our data provide evidence that Raf-1 siRNA may be an effective strategy for reducing tumor growth.
Leng
Qixin
Q
Department of Pathology, University of Maryland Baltimore, MSTF Building, 10 South Pine Street, Baltimore, Maryland 21201, USA.
Mixson
Archibald James
AJ
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D005260:Female; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D019908:Proto-Oncogene Proteins c-raf / Q000037:antagonists & inhibitors* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000037:antagonists & inhibitors; D012334:RNA, Neoplasm / Q000378:metabolism; D034741:RNA, Small Interfering / Q000627:therapeutic use*; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D019908:Proto-Oncogene Proteins c-raf