Suppression of survivin expression inhibits in vivo tumorigenicity and angiogenesis in gastric cancer.
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.
Tu
Shui Ping
SP
Department of Gastroenterology, Rui-jin Hospital, Shanghai Second Medical University, Shanghai, People's Republic of China.
Jiang
Xiao Hua
XH
Lin
Marie C M
MC
Cui
Jian Tao
JT
Yang
Yi
Y
Lum
Ching Tung
CT
Zou
Bing
B
Zhu
Yan Bo
YB
Jiang
Shi Hu
SH
Wong
Wai Man
WM
Chan
Annie On-On
AO
Yuen
Man Fung
MF
Lam
Shiu Kum
SK
Kung
Hsiang Fu
HF
Wong
Benjamin Chun-Yu
BC
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
C107489:BIRC5 protein, human; D016373:DNA, Antisense; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin