Inhibition of human cancer-cell proliferation by long double-stranded RNAs.

Abstract

Three different enzymatically synthesized long double-stranded RNAs (dsRNAs) [448 bp homologous to the third exon of c-myc messenger RNA (mRNA) (dsMyc); 473 bp homologous to enhanced green fluorescent protein (EGFP) mRNA (dsEGFP) and control interferon inducer poly(I:C)] were studied for antiproliferative and gene-silencing activities in KB-3-1, SK-N-MC, and IMR-32 human cancer cell lines. Simple incubation with these dsRNAs did not affect the expression of c-myc gene and the proliferation of KB-3-1 and IMR-32 cells, but inhibited the proliferation of SK-N-MC cells. Transfection of KB-3-1 and SK-N-MC cells using Oligofectamine-dsRNAs complexes resulted in dose-dependent inhibition of c-myc and beta-actin genes expression and proliferation. The data show that dsMyc, acting both as interferon inducer and as gene-specific interfering RNA, is more effective as c-myc inhibitor than other tested dsRNAs. The most efficient inhibition of proliferation was displayed by dsEGFP RNA, dsMyc and poly(I:C) were effective only when used in higher concentrations. Our data indicate that transfection of studied dsRNAs causes an increase in apoptotic and dead cells number in the cell population. This proapoptotic activity correlates with dsRNAs-induced antiproliferative activity. However the difference in cell growth between dsRNA-treated and Oligofectamine-only treated cells can not be attributed only to the loss of cells due to the apoptosis; it also indicates some retardation of cell cycle progression caused by dsRNA.