Antitumor effect of palmitic acid‐conjugated Dsi RNA for colon cancer in a mouse subcutaneous tumor model

In this study, we synthesized Dicer‐substrate si RNA conjugated with palmitic acid at the 5′‐end of the sense strand (C16‐Dsi RNA ), and examined its RNA i effect on β‐catenin as a target gene in a colon cancer cell line, HT 29Luc, both in vitro and in vivo. We examined the in vitro RNA i effect in HT 29Luc cells and found that C16‐Dsi RNA strongly inhibited expression of the β‐catenin gene in comparison with non‐modified Dsi RNA . Also, high membrane permeability of C16‐Dsi RNA was exhibited, and it was confirmed that most of the C16‐Dsi RNA was localized in cytoplasm of HT 29Luc cells. In regard to the in vivo RNA i effect, C16‐Dsi RNA complexed with Invivofectamine targeting the β‐catenin gene was locally administered to a subcutaneous tumor formed by implantation of HT 29Luc cells into the subcutis of nude mice; we evaluated the effect by measuring the bioluminescence increase, which reflects tumor growth, using an in vivo imaging system. As a result, C16‐Dsi RNA strongly inhibited the growth of tumors formed in subcutis of nude mice compared with non‐modified Dsi RNA , and this in vivo RNA i effect lasted up to 15 days. Our results suggest that C16‐Dsi RNA should be vigorously pursued as a novel nucleic acid medicine for clinical treatment of cancer.