Antisense DNA를 사용한 Cdk2조절에 의한 암세포의 성장 억제

Abstract

Cancer is characterized by deregulated cell cycle. Recent studies on cell cycle have demonstrated that some proteins, which regulate cell proliferation, may also be involved in oncogenesis. Critical transitions in a cell cycle are regulated by sequential activation of a series of cyclins and cyclin-dependent kinases (Cdks). Cdks are catalytic subunits of a family of serine/threonine protein kinase complexes, and are involved in the progression of cell cycle at various stages through G1, S, G2 and M phases. Cdk2 is essential for transition from G1 to S phase of mammalian cell cycle and overexpressed in cancer cells. In this study, we examined the effects of antisense to Cdk2 with a novel structure. Circular antisense, targeting a large area containing the translation start site of the Cdk2 cDNA, was constructed. When HeLa cells were treated with Cdk2 antisense, dose-dependent decrease of Cdk2 mRNA was observed. Cancer cell growth was found to be inhibited by more than 50% determined by cell counting assays. However, cell growth was not significantly inhibited, when treated with sense and control single strand DNA. These results suggest that Cdk2 plays an important role in the cancer cell proliferation and circular antisense DNA can be employed in the development of molecular antisense drugs for cancer.