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-μ M 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.
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We are grateful to Sayuko Kaminosono, Haruna Yamanami, and Kotaro Oka (Faculty of Science and Technology, Keio University, Kohoku-ku, Yokohama, Japan) for their kind help with the experiments and for providing the laboratory environment for this study. This study was supported by Special Coordination Funds for Promoting Science and Technology from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and from Keio University's 21st Century COE Program for Understanding and Control of Life Function via Systems Biology.
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Hiroi, N., Funahashi, A. & Kitano, H. Comparative studies of suppression of malignant cancer cell phenotype by antisense oligo DNA and small interfering RNA. Cancer Gene Ther 13, 7–12 (2006). https://doi.org/10.1038/sj.cgt.7700869
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