Abstract
Our study investigated the effects of antisense oligodeoxynucleotide targeting survivin on human gastric cancer cells. Human gastric cancer cells were incubated with antisense oligodeoxynucleotide targeting survivin for pre-designed durations, and then the cell growth was observed under light and electronic microscopes. Electrophoresis of fractured DNA fragments was performed to detect the DNA distribution and telomere repeat amplification protocol (TRAP) was used for the detection of telomerase activity. Antisense oligodeoxynucleotide targeting survivin could induce the apoptosis of human gastric cancer cells which were characterized by plasma membrane blistering, chromatin condensation, nuclear fragmentation, and formation of apoptotic bodies. Electrophoresis showed characteristic DNA ladder. Flow cytometry revealed hypo-diploid apoptosis peak before G1 phase and the telomerase activity was significantly inhibited. These results demonstrated antisense oligodeoxynucleotide targeting survivin can induce the apoptosis of gastric cancer cells to inhibit their proliferation.
Highlights
Studies have confirmed that the occurrence and development of cancers have the involvement of a complex cancer-related gene network, the changes in the functions of these genes share the consequence that cells develop uncontrolled proliferation and disruption of apoptosis
Survivin is a new member of inhibitor of apoptosis protein (IAP), has high expression in cancers and can exert anti-apoptotic effect (Ambrosini et al, 1997; Mesri et al, 2010)
After treatment with Antisense oligonucleotide targeting survivin (ASODN) at different concentrations, the cell growth was inhibited to different extents, which was in a time and concentration dependent manner
Summary
Studies have confirmed that the occurrence and development of cancers have the involvement of a complex cancer-related gene network, the changes in the functions of these genes share the consequence that cells develop uncontrolled proliferation and disruption of apoptosis. Survivin is a new member of inhibitor of apoptosis protein (IAP), has high expression in cancers and can exert anti-apoptotic effect (Ambrosini et al, 1997; Mesri et al, 2010). Survivin is a newly identified anti-apoptotic molecule and its over-expression is frequently observed in cancers. The development and application of survivin signaling pathway are beneficial for the early diagnosis of cancers and the determination of prognosis of cancer patients and provide new targets for the biotherapy of cancers. Antisense oligonucleotide targeting survivin (ASODN) can induce the apoptosis of hepatic cancer cells and inhibit their growth (Grossman et al, 2006; Altieri and Marchisio, 2006; Tanabe et al, 2006). Survivin ASODN was transfected into human gastric cancer cells and the anti-tumor effects were observed. Our findings may provide theoretical and experimental bases for the treatment of gastric cancer
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