Survivin antisense oligodeoxynucleotide inhibits growth of gastric cancer cells.
OBJECTIVE
To investigate the effect of transfected survivin antisense oligonucleotide (ASODN) on proliferation and apoptosis of gastric cancer cells.


METHODS
The authors designed ASODNs targeting different regions of survivin mRNA, including surviving ASODN1, ASODN2 and ASODN3. ASODNs were transfected into gastric cancer cell line SGC 7901, cell growth was detected by MTT assay. Cells exposed to the potent oligonucleotide were also examined for apoptosis induction by FCM and fluorescence microscopy. Semiquantitive RT-PCR and Western blot examinations were carried for expression of survivin mRNA and protein.


RESULTS
ASODN3 caused a statistically significant reduction of cell viability to 60.6% (+/-2.9%) (P<0.01), while ASODN1 and ASODN2 had no such changes (P>0.05). The cell growth was also significantly inhibited by ASODN3, compared with reversal and scrambled sequence. A significant loss of survivin mRNA was presented in ASODN3 treated cells and this was not seen in treatment with sense ODN or scramble ODN. Protein level was significantly decreased 48 h after survivin ASODN trasfected by approximately 2-fold decrease compared with untreated controls. However, ASODN3 did not induce significant apoptosis response until 48 h after transfection (P>0.05).


CONCLUSIONS
ASODN3, which targets translation initiation part, can be identified as a most potent antisense compound. Srvivin ASODN3 may provide a novel approach to therapy of gastric cancer.
Yang
Jian-Hui
JH
Department of Oncological Surgery, Shidong Hospital, Ningguo Road 236, Shanghai 20090, China. yangjianhuicn@sohu.com
Zhang
Yi-Chu
YC
Qian
Hui-Qing
HQ
D017209:Apoptosis; D002455:Cell Division; D045744:Cell Line, Tumor / Q000166:cytology; D015870:Gene Expression; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D009363:Neoplasm Proteins; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D013274:Stomach Neoplasms; D000077022:Survivin; D014162:Transfection
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D000077022:Survivin