title: Downregulation of survivin expression exerts antitumoral effects on mouse breast cancer cellsin vitroandin vivo.
abstract: Metastasis constantly occurs in the majority of cases of primary breast cancer at late stage or following surgical treatment. Survivin, a member of the inhibitor of apoptosis protein family, has long been recognized as a promising anticancer target, but its antitumor effects remain largely unexplored. In order to elucidate the role of survivin in breast cancer metastasis, short interfering RNA (siRNA) was used in the present study to specifically downregulate survivin expression in the murine breast cancer cell line 4T1. The results demonstrated that blocking the expression of survivin by siRNA inhibited the proliferation, migration and invasion abilities of murine breast cancer cellsin vitro. Vascular endothelial growth factor (VEGF)-C is a lymphatic endothelial cell-stimulating factor that may lead to the formation of lymphatic vessels in lymph nodes. In the present study, the inhibition of survivin by siRNA was able to reduce the overexpression of VEGF-C in 4T1 cells. Furthermore, intratumoral injections of the survivin-siRNA significantly inhibited the growth of orthotopically transplanted 4T1 tumorsin vivo. In addition, the number of pulmonary metastases and the microlymphatic vessel density were significantly reducedin vivo, following transfection with survivin-siRNA. The results of the present study suggested that the Akt/hypoxia-inducible factor-1α signaling pathway participates in the survivin-mediated downregulation of VEGF-C expression observed in breast cancer cells treated with survivin-siRNA. Therefore, the use of siRNA specifically targeting survivin may be a potential anticancer method in the future.
authors: Department of Biochemistry and Molecular Biology, Medical College, Qingdao University, Qingdao, Shandong 266021, P.R. China; Institute of Transfusion Medicine, Qingdao Blood Center, Qingdao, Shandong 266071, P.R. China.
authors: Wen-Hui
authors: WH
authors: Ma
authors: Department of Biochemistry and Molecular Biology, Medical College, Qingdao University, Qingdao, Shandong 266021, P.R. China.
authors: Yong-Chao
authors: YC
authors: Liu
authors: Department of Biochemistry and Molecular Biology, Medical College, Qingdao University, Qingdao, Shandong 266021, P.R. China.
authors: Mei-Lan
authors: ML
authors: Xue
authors: Department of Biochemistry and Molecular Biology, Medical College, Qingdao University, Qingdao, Shandong 266021, P.R. China.
authors: Zheng
authors: Z
authors: Zheng
authors: Department of Biochemistry and Molecular Biology, Medical College, Qingdao University, Qingdao, Shandong 266021, P.R. China.
authors: Yin-Lin
authors: YL
authors: Ge
keywords: VEGF-C; breast cancer; migration; short interfering RNA; survivin; tumor inhibition