Anti-K-Ras siRNA to treat pancreatic cancer

Daniel C. Julien, Anjil Giri, Madhusudhan Papasani, Gordon Murdoch, Patrick Hrdlicka, Rodney A. Hill

    Research output: Book chapter/Published conference paperConference paperpeer-review

    Abstract

    Four pancreatic cancer cell lines with the same point mutation at the 12th codon (GGT > GAT) of the K-Ras oncogene were used in this study: Pancl and Panc 8.13 are both homozygous for mutant K-Ras (mK-Ras), Panc 10.05 is heterozygous for the mutation, and BXPC3 possesses both wild-type K-Ras (wK-Ras) alleles. Cells were transfected with Lipofectamine and either scrambled siRNA or mK-Ras siRNA for a period of six hours. Total K-Ras gene expression in these cells was then quantified at 24, 48, or 72 h after transfection by qPCR using wK-Ras and mK-Ras-specific primers. Results from these experiments show a significant down-regulation of mK-Ras compared to cells transfected with scrambled siRNA. After 24 h of treatment, Pancl, Panc 8.13, and Panc 10.05 cells showed significant down-regulation of mK-Ras mRNA, 52%, 50%, and 48% less, respectively, compared to scrambled siRNA control. On the other hand, results for BXPC3, the wK-Ras cell line, showed no significant change in wK-Ras mRNA throughout all time-points. Additionally, mK-Ras siRNA appears to significantly inhibit cell metabolic activity. These findings suggest that RNAi directed against point mutations in the K-Ras oncogene may be an effective method of to inhibit progression of pancreatic tumors. However, additional studies of nanoparticles-based siRNA delivery platforms are still required in order to determine if this approach can address the issue of intracellular delivery as well as to establish the potency of gene knockdown in such a system.

    Original languageEnglish
    Title of host publicationNanotechnology 2010
    Subtitle of host publicationBio Sensors, Instruments, Medical, Environment and Energy - Technical Proceedings of the 2010 NSTI Nanotechnology Conference and Expo, NSTI-Nanotech 2010
    Pages401-404
    Number of pages4
    Publication statusPublished - 09 Nov 2010
    EventNanotechnology 2010: Bio Sensors, Instruments, Medical, Environment and Energy - 2010 NSTI Nanotechnology Conference and Expo, NSTI-Nanotech 2010 - Anaheim, CA, United States
    Duration: 21 Jun 201024 Jun 2010

    Publication series

    NameNanotechnology 2010: Bio Sensors, Instruments, Medical, Environment and Energy - Technical Proceedings of the 2010 NSTI Nanotechnology Conference and Expo, NSTI-Nanotech 2010
    Volume3

    Conference

    ConferenceNanotechnology 2010: Bio Sensors, Instruments, Medical, Environment and Energy - 2010 NSTI Nanotechnology Conference and Expo, NSTI-Nanotech 2010
    Country/TerritoryUnited States
    CityAnaheim, CA
    Period21/06/1024/06/10

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