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

Tu, Shui Ping; Jiang, Xiao Hua; Lin, Marie C M; Cui, Jian Tao; Yang, Yi; Lum, Ching Tung; Zou, Bing; Zhu, Yan Bo; Jiang, Shi Hu; Wong, Wai Man; Chan, Annie On-On; Yuen, Man Fung; Lam, Shiu Kum; Kung, Hsiang Fu; Wong, Benjamin Chun-Yu.
Cancer Res; 63(22): 7724-32, 2003 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-14633697
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.
Selo DaSilva