Stable RNA interference of ErbB-2 gene synergistic with epirubicin suppresses breast cancer growth in vitro and in vivo

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• 作者：Xiaoqu Hu ; Fengxi Su ; Li Qin ; Weijuan Jia ; Chang Gong ; Fengyan Yu ; Jujiang Guo and Erwei Song
• 关键词：Her2 ; Breast cancer ; RNA interference ; Plasmid vector ; Chemotherapy ; Anthracycline ; Apoptosis
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2006
• 出版时间：4 August 2006
• 年：2006
• 卷：346
• 期：3
• 页码：778-785
• 全文大小：242 K

文摘

Overexpression of human epidermal growth factor receptor-2 (Her2, ErbB-2) contributes to the progression and metastasis of breast cancer, implying that Her2 gene is a suitable target of RNA interference (RNAi) for breast cancer therapy. Here, we employed plasmid-mediated expression of 2 different Her2-shRNAs (pU6-Her2shRNAs) efficiently silenced the target gene expression on Her2 expressing SKBR-3 breast cancer cells in both mRNA and protein levels. Consequently, pU6-Her2shRNA increased apoptosis and reduced proliferation of SKBR-3 cells assayed by TUNEL and MTT, respectively. In vivo, intra-tumor injection of pU6-Her2shRNA inhibited the growth of SKBR-3 tumors inoculated subcutaneously in nude mice. Furthermore, pU6-Her2shRNA synergized the tumor suppression effect of epirubicin to SKBR-3 cells in vitro and implanted subcutaneously in nude mice. Therefore, we concluded that stable silencing of Her2 gene expression with plasmid expressing shRNA may hold great promise as a novel therapy for Her2 expressing breast cancers alone or in combination with anthracycline chemotherapy.