NSTI BioNano 2010

Anti-K-Ras siRNA to Treat Pancreatic Cancer

D.C. Julien, A. Giri, M. Papasani, G. Murdoch, P. Hrdlicka, R.A. Hill
University of Idaho, US

Keywords: pancreatic cancer, K-Ras, siRNA

Abstract:

Cancer of the pancreas is a leading cause of cancer-related mortality. Chemotherapeutic drugs used to treat pancreatic cancers are toxic and minimally effective, yielding a 1-4% 5-year survival rate after initial diagnosis. Approximately 90% of pancreatic cancers possess point mutations in the K-Ras proto-oncogene. Point mutations in the K-Ras gene cause the K-Ras protein to become stuck in the “on” GTP bound conformation, leading to constitutive activation. Small interfering RNA (siRNA) against mutated K-Ras (mK-Ras) may be a potential therapeutic option for the treatment of pancreatic cancers. In this study, four pancreatic cancer cell lines were used: two that are homozygous for an mK-Ras point mutation, one that is heterozygous and one that has the wild genotype (wK-Ras). Cells were transfected with Lipofectamine and either scrambled siRNA or mK-Ras siRNA and K-Ras gene expression quantified at 24, 48, or 72 h after transfection. Data from mK-Ras genotypes showed a significant down-regulation of mK-Ras compared to cells transfected with scrambled siRNA. Data for the wK-Ras cell line, showed no significant change in wK-Ras mRNA throughout all time-points. These data provide initial proof-of-priciple that siRNA may be a successful treatment for knockdown of mK-Ras and may serve as a valid approach to treating cancers with K-Ras point mutations.
 
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