TY - JOUR
T1 - Antitumor effect of palmitic acid-conjugated DsiRNA for colon cancer in a mouse subcutaneous tumor model
AU - Kubo, Takanori
AU - Nishimura, Yoshio
AU - Hatori, Yuta
AU - Akagi, Reiko
AU - Mihara, Keichiro
AU - Yanagihara, Kazuyoshi
AU - Seyama, Toshio
N1 - Funding Information:
This work was financially supported by JSPS KAKENHI Grant Number JP16K01939, JP16K08335 and JP17K18289.
Publisher Copyright:
© 2018 John Wiley & Sons A/S
PY - 2019/4
Y1 - 2019/4
N2 - In this study, we synthesized Dicer-substrate siRNA conjugated with palmitic acid at the 5′-end of the sense strand (C16-DsiRNA), and examined its RNAi effect on β-catenin as a target gene in a colon cancer cell line, HT29Luc, both in vitro and in vivo. We examined the in vitro RNAi effect in HT29Luc cells and found that C16-DsiRNA strongly inhibited expression of the β-catenin gene in comparison with non-modified DsiRNA. Also, high membrane permeability of C16-DsiRNA was exhibited, and it was confirmed that most of the C16-DsiRNA was localized in cytoplasm of HT29Luc cells. In regard to the in vivo RNAi effect, C16-DsiRNA complexed with Invivofectamine targeting the β-catenin gene was locally administered to a subcutaneous tumor formed by implantation of HT29Luc 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-DsiRNA strongly inhibited the growth of tumors formed in subcutis of nude mice compared with non-modified DsiRNA, and this in vivo RNAi effect lasted up to 15 days. Our results suggest that C16-DsiRNA should be vigorously pursued as a novel nucleic acid medicine for clinical treatment of cancer.
AB - In this study, we synthesized Dicer-substrate siRNA conjugated with palmitic acid at the 5′-end of the sense strand (C16-DsiRNA), and examined its RNAi effect on β-catenin as a target gene in a colon cancer cell line, HT29Luc, both in vitro and in vivo. We examined the in vitro RNAi effect in HT29Luc cells and found that C16-DsiRNA strongly inhibited expression of the β-catenin gene in comparison with non-modified DsiRNA. Also, high membrane permeability of C16-DsiRNA was exhibited, and it was confirmed that most of the C16-DsiRNA was localized in cytoplasm of HT29Luc cells. In regard to the in vivo RNAi effect, C16-DsiRNA complexed with Invivofectamine targeting the β-catenin gene was locally administered to a subcutaneous tumor formed by implantation of HT29Luc 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-DsiRNA strongly inhibited the growth of tumors formed in subcutis of nude mice compared with non-modified DsiRNA, and this in vivo RNAi effect lasted up to 15 days. Our results suggest that C16-DsiRNA should be vigorously pursued as a novel nucleic acid medicine for clinical treatment of cancer.
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U2 - 10.1111/cbdd.13454
DO - 10.1111/cbdd.13454
M3 - Article
C2 - 30560565
AN - SCOPUS:85059911734
VL - 93
SP - 570
EP - 581
JO - Chemical Biology and Drug Design
JF - Chemical Biology and Drug Design
SN - 1747-0277
IS - 4
ER -