Suppression of colorectal cancer growth using an adenovirus vector expressing an antisense K-ras RNA

Molecular Therapy : the Journal of the American Society of Gene Therapy
M NakanoT Yoshida

Abstract

In human colorectal cancer, K-ras point mutations occur in approximately 40-50% of the cases, a frequency second only to pancreatic cancer (80-90%). Unlike pancreatic and lung cancers, however, the tumor-suppressive effect of antisense K-ras RNA expression has not been examined for colorectal cancers. A recombinant adenovirus vector expressing an antisense or sense K-ras gene fragment (AxCA-AS-K-ras or AxCA-S-K-ras) was first transduced into seven human colorectal cancer cell lines. Stable expression of antisense or sense K-ras RNA was detected by RNA blot analysis. Western blot analysis confirmed a reduction of up to 25% of K-ras-specific p21 protein in the antisense K-ras-transduced HCT-15 cells. In contrast to our previous findings on pancreatic cancer, the status of K-ras point mutations was not correlated with the growth-suppressive effect of the antisense K-ras vector: both the K-ras-mutation-positive and -negative colorectal cancer cell lines were suppressed for their growth in vitro. There was no growth-inhibitory effect on normal cells such as hepatocytes. Next, to test the efficacy in vivo, HCT-15 cells were inoculated subcutaneously into the left flank of SCID mice, and AxCA-AS-K-ras was injected intratumorally three...Continue Reading

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Citations

Mar 31, 2015·Artificial Cells, Nanomedicine, and Biotechnology·Ying ZhangYong Sun
Apr 10, 2004·Cancer Science·Teruhiko YoshidaKazunori Aoki
Sep 19, 2003·Biochemical and Biophysical Research Communications·Shumpei OhnamiTeruhiko Yoshida
Dec 15, 2010·Journal of Hepatology·Maria A González-CarmonaWolfgang H Caselmann
Sep 29, 2004·The Journal of Gene Medicine·Kazuteru HatanakaKazunori Aoki

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