Suppression of survivin expression inhibits in vivo tumorigenicity and angiogenesis in gastric cancer.

Abstract	Survivin plays an important role in cancer development. We aim to show here that suppression of survivin expression or function by antisense and dominant-negative (DN) mutant can inhibit gastric cancer carcinogenesis and angiogenesis in vivo. Plasmid constructs expressing survivin antisense and DN mutant replacing the cysteine residue at amino acid 84 with alanine (Cys84Ala) were prepared and introduced into BCG-823 and MKN-45 gastric cancer cells to establish stable transfectants. We showed that both antisense and DN mutant stable transfectants exhibited abnormal morphology, with decreased cell growth and increased rate of spontaneous apoptosis and mitotic catastrophe. Furthermore, in nude mice xenografts, these cells exhibited decreased de novo gastric tumor formation and reduced development of angiogenesis. Results from these studies strongly suggest that survivin is a promising target for gastric cancer treatment.
Authors	Shui Ping Tu, Xiao Hua Jiang, Marie C M Lin, Jian Tao Cui, Yi Yang, Ching Tung Lum, Bing Zou, Yan Bo Zhu, Shi Hu Jiang, Wai Man Wong, Annie On-On Chan, Man Fung Yuen, Shiu Kum Lam, Hsiang Fu Kung, Benjamin Chun-Yu Wong
Journal	Cancer research (Cancer Res) Vol. 63 Issue 22 Pg. 7724-32 (Nov 15 2003) ISSN: 0008-5472 [Print] United States
PMID	14633697 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	BIRC5 protein, human DNA, Antisense Inhibitor of Apoptosis Proteins Microtubule-Associated Proteins Neoplasm Proteins Survivin
Topics	Adenocarcinoma (blood supply, genetics, pathology, therapy) Animals Apoptosis (genetics) Cell Division (genetics) Cell Line, Tumor DNA, Antisense (genetics) Female Humans Inhibitor of Apoptosis Proteins Mice Mice, Inbred BALB C Mice, Nude Microtubule-Associated Proteins (antagonists & inhibitors, biosynthesis, genetics) Neoplasm Proteins Neovascularization, Pathologic (genetics, therapy) Stomach Neoplasms (blood supply, genetics, pathology, therapy) Survivin Transfection Xenograft Model Antitumor Assays

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