Silencing of Her2 CCNB1 and PKC Genes by siRNA Results in ProlongedRetardation of Neuroblastoma Cell Division

摘要

Deregulation of the expression of the genes that are involved in the control of the cell cycle impairs cellular differentiation and leads to cell death. This process can result in uncontrollable cell proliferation and, subsequently, cancer development. In this study, we examined the effect of the silencing of cancer-related genes by small interfering RNAs (siRNA) targeted at mRNAof Her2, cyclin B1 (CCNB1), and protein kinase C(PKC) on the proliferation of human cancer cells of different origins. Maximum silencing ofCCNB1,Her2(in KB-3-1, SK-N-MC, MCF-7 cells), andPKC(in MCF-7 cells) was achieved 72 h after transfection of the corresponding siRNAs, and 12 days after the transfection, the initial levels of the target mRNAs were fully recovered. Silencing ofHer2,CCNB1,andPKCdifferently effected the proliferation of the cell lines under study. The most pronounced antiproliferative action of the investigated siRNAs was observed in neuroblastoma SK-N-MC cells (3 – 10-fold reduction in the proliferation rate) even after the recovery of the initial levels of expressionofthe Her2,CCNB1,andPKС genes. The obtained data indicatethat theCCNB1 andPKCgenes can be used astargets in the development of drugs for neuroblastoma treatment.