[Small interference RNAs directed against KDR gene inhibit the proliferation of breast cancer cells in vitro and in vivo].
OBJECTIVE
To inhibit kinase insert domain-containing receptor (KDR) expression chemically modified siRNA in vitro and in vivo and to investigate the feasibility and specificity of gene therapy for breast cancer.


METHODS
In vitro, siRNA was transfected into MCF-7 cells to induce RNAi by using cationic liposome Lipofectamine2000(TM). The changes of KDR mRNA and protein expression in both siRNA treatment group and control group were measured by MTT assay and RT-PCR, In vivo, the siRNA was transfected into transplanted tumor in nude mice by using cationic polymer nanoparticle In vivo jetPEI(TM). Tumor growth was observed. The mRNA and protein expression of KDR was measured by RT-PCR and immunohistochemical staining.


RESULTS
Experiments in vitro showed that siRNA directed against KDR effectively inhibited the proliferation of MCF-7 cells and downregulated KDR mRNA expression. In vivo, the growth of tumor was visibly suppressed. Furthermore, RT-PCR and immunohistochemical results indicated that KDR mRNA and protein expression was reduced in excised tumors.


CONCLUSIONS
RNAi mediated by chemically modified siRNA markedly decreased KDR gene expression and inhibited cellular proliferation. It may have the potential as a therapeutic method to treat human cancer.
Zhang
Xiao-jing
XJ
Department of Biochemistry and Molecular Biology, Medical College, Qingdao University, Qingdao 266021, China. bunnybay@126.com
Ge
Yin-lin
YL
Hou
Lin
L
Li
Quan
Q
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D020868:Gene Silencing / Q000187:drug effects* / Q000502:physiology; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008207:Lymphatic Metastasis / Q000532:radiotherapy*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D034622:RNA Interference / Q000187:drug effects*; D034741:RNA, Small Interfering / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*; D023041:Xenograft Model Antitumor Assays
D034741:RNA, Small Interfering; D040301:Vascular Endothelial Growth Factor Receptor-2