Original Article

Cancer Gene Therapy (2006) 13, 7–12. doi:10.1038/sj.cgt.7700869; published online 5 August 2005

Comparative studies of suppression of malignant cancer cell phenotype by antisense oligo DNA and small interfering RNA

N Hiroi1,2,3,4,6, A Funahashi1,2,3,4,7 and H Kitano1,2,3,4,5

  1. 1ERATO-SORST, Kitano Symbiotic Systems Project, Japan Science and Technology Agency, Shibuya-ku, Tokyo, Japan
  2. 2Faculty of Science and Technology, Keio University, Kohoku-ku, Yokohama, Japan
  3. 3School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan
  4. 4The Systems Biology Institute, Shibuya-ku, Tokyo, Japan
  5. 5Sony Computer Science Laboratories, Inc., Shinagawa, Tokyo, Japan

Correspondence: Dr N Hiroi, JST ERATO-SORST, Kitano Symbiotic Systems Project, 6-31-15 Jingumae, M-31 Suite 6A, Shibuya-ku, Tokyo 150-0001, Japan. E-mail: nhiroi@symbio.jst.go.jp

6Visiting research fellow of Keio University for the period 1 June 2002–31 March 2006.

7Visiting research fellow of Keio University for the period 1 January 2004–31 March 2006.

Received 9 June 2004; Revised 27 March 2005; Accepted 11 April 2005; Published online 5 August 2005.

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Abstract

One of the distinguishing features of malignant tumor cells is the ability to proliferate in an anchorage-independent manner; methods that effectively suppress this phenotype may be applicable to the therapeutic inhibition of the malignancy of cancers. Interfering RNA is a potentially powerful tool for cancer therapy because of its specificity of target selection and remarkably high efficiency in target mRNA suppression. We studied the use of two knockdown strategies, antisense oligo DNA (AS-ODN) and small interfering RNA (siRNA), and showed how the anchorage-independent proliferation of malignant cells could be blocked efficiently. Anchorage-independent proliferation of rat fibroblasts transformed with v-src was suppressed with only a single 1-muM dose of AS-ODN; similar suppression using siRNA required treatment with 1 nM siRNA every 12 h. With our experimental system, the molecular stability of AS-ODN allowed the use of a simple treatment regimen to control the amount of the target molecule, providing that the treatment dose was sufficiently high. In comparison, siRNA treatment was effective at lower doses, but more frequent treatment was necessary to achieve the same suppression of proliferation.

Keywords:

anchorage-independent growth, antisense oligo DNA, small interfering RNA