Inhibition of colon cancer cell proliferation by antisense oligonucleotides targeting the messenger RNA of the Ki-ras gene.

Point mutations that activate the Ki-ras proto-oncogene are present in approximately 50% of human colorectal tumors and the activated Ki-ras gene is considered to play an important role in colorectal cancer cell proliferation. Five different colon cancer cell lines and two kinds of control cell lines were treated with antisense oligonucleotides complementary to the messenger RNA of Ki-ras. Treatment with antisense oligonucleotides at concentrations between 10 and 40 microM significantly and dose-dependently inhibited cell growth, colony formation and Ki-ras protein production of the colon cancer cells with activated Ki-ras, but did not affect the normal cells and colon cancer cells without Ki-ras mutation. These results show that use of synthetic oligonucleotides is an effective way of producing antisense-mediated changes in the behavior of human colon cancer cells with an activated Ki-ras gene.