title: 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: Department of Gastroenterology, Rui-jin Hospital, Shanghai Second Medical University, Shanghai, People's Republic of China.
authors: Shui Ping
authors: SP
authors: Tu
authors: Xiao Hua
authors: XH
authors: Jiang
authors: Marie C M
authors: MC
authors: Lin
authors: Jian Tao
authors: JT
authors: Cui
authors: Yi
authors: Y
authors: Yang
authors: Ching Tung
authors: CT
authors: Lum
authors: Bing
authors: B
authors: Zou
authors: Yan Bo
authors: YB
authors: Zhu
authors: Shi Hu
authors: SH
authors: Jiang
authors: Wai Man
authors: WM
authors: Wong
authors: Annie On-On
authors: AO
authors: Chan
authors: Man Fung
authors: MF
authors: Yuen
authors: Shiu Kum
authors: SK
authors: Lam
authors: Hsiang Fu
authors: HF
authors: Kung
authors: Benjamin Chun-Yu
authors: BC
authors: Wong
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D045744:Cell Line, Tumor; D016373:DNA, Antisense / Q000235:genetics*; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics*; D009363:Neoplasm Proteins; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000628:therapy*; D013274:Stomach Neoplasms / Q000098:blood supply / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D000077022:Survivin; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: C107489:BIRC5 protein, human; D016373:DNA, Antisense; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin