title: Chemically modified siRNA directed against the KDR gene inhibits the proliferation of breast cancer cells.
abstract: Vascular endothelial growth factor receptor-2 or kinase insert domain-containing receptor (VEGFR2/KDR) is secreted by most solid tumors, including breast cancer, and is an important mediator of angiogenesis. To observe the effects of KDR gene expression on cell proliferation and the cell cycle in MCF-7 cells in vitro and in vivo, we used chemically modified siRNA directed against KDR. The results revealed that chemically modified siRNA transfection of the KDR gene effectively inhibited the proliferation of MCF-7 cells, arrested cells in the G1 phase and down-regulated the expression of KDR. In addition, in the progression of cell cycle arrest induced by siRNA, phosphorylated ERK and CDK1 expression was down-regulated (P<0.01). In vivo, the growth of tumors was visibly suppressed. RT-PCR and the results of immunohistochemistry indicated that KDR mRNA and protein expression was reduced in the excised tumors. In contrast, there were no obvious changes in the control groups. This implies that chemically modified KDR siRNA markedly decreases KDR gene expression and inhibits cellular proliferation in vitro, as well as suppressing tumor growth in a xenograft model. KDR may be a new target for breast cancer treatment.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical College, Qingdao University, Shandong 266021, P.R. China. geyinlin@126.com.
authors.forename: Yin-Lin
authors.initials: YL
authors.lastname: Ge
authors.forename: Jin-Yu
authors.initials: JY
authors.lastname: Zhang
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Hou
authors.forename: Quan
authors.initials: Q
authors.lastname: Li
authors.forename: Mei-Lan
authors.initials: ML
authors.lastname: Xue