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Published on: May 11, 2018
+Antisense oligonucleotide targeting survivin inhibits growth by inducing apoptosis in human osteosarcoma cells MG-63
1Department of Orthopaedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.
Unlabelled:
Survivin may play an important role in the development of osteosarcoma. In this study, we chose osteosarcoma cell line MG-63, which highly expressed survivin, to observe the effects of antisense oligonucleotide targeting survivin on the apoptosis induction and proliferation inhibition. It was shown in our results that the apoptosis rate and the proliferation inhibition rate increased significantly in survivin-positive cells MG-63 by using MTT and flow cytometry methods. We found that the growth inhibition rate and apoptosis rate were changed in a dose-dependent way. When the concentration of antisurvivin oligonucleotide was 600 nM, the effects reached the peak. RT-PCR and western-blot methods were used to detect the mRNA and protein expression of survivin in MG-63. We observed that the mRNA and protein expression of survivin reduced after transfected with antisurvivin oligonucleotides at the concentration of 200 nM, 400 nM and 600 nM. At the same time, we found that the mRNA and protein expression of Fas were up-regulated with the concentration of antisurvivin oligonucleotides from 200 nM to 600 nM. It was negative associated with the expression change of survivin. These data suggested that survivin should play an important role in the development of osteosarcoma and the survivin blockaded by using antisurvivin oligonucleotide could inhibit the proliferation and induce apoptosis of osteosarcoma by decreasing the expression of survivin and activate the Fas-mediated apoptosis. Down-regulation of survivin by antisense oligonucleotide might be an effective strategy to the treatment of osteosarcoma and might improve the therapeutic effect.
Keywords:
osteosarcoma, Survivin, apoptosis, Fas.
Insights
Targeting the protein survivin with antisense oligonucleotides significantly inhibits osteosarcoma cell proliferation and induces apoptosis. This approach down-regulates survivin expression and activates Fas-mediated apoptosis, suggesting a potential therapeutic strategy for osteosarcoma.
Area of Science:
- Oncology
- Molecular Biology
Background:
- Osteosarcoma is a primary bone malignancy.
- Survivin is implicated in the development and progression of various cancers, including osteosarcoma.
- Apoptosis and Fas signaling pathways are critical in cancer cell fate.
Purpose of the Study:
- To investigate the effect of targeting survivin using antisense oligonucleotides on osteosarcoma cell apoptosis and proliferation.
- To elucidate the mechanism by which survivin influences osteosarcoma progression.
Main Methods:
- Utilized the osteosarcoma cell line MG-63, which exhibits high survivin expression.
- Employed MTT assays and flow cytometry to assess apoptosis and proliferation rates.
- RT-PCR and Western blotting were used to measure survivin and Fas mRNA and protein expression.
Main Results:
- Antisense oligonucleotides targeting survivin significantly increased apoptosis and inhibited proliferation in MG-63 cells in a dose-dependent manner.
- Survivin mRNA and protein levels were reduced following transfection with antisurvivin oligonucleotides.
- Fas mRNA and protein expression were upregulated in a dose-dependent manner, inversely correlating with survivin expression.
Conclusions:
- Survivin plays a crucial role in osteosarcoma development.
- Blocking survivin with antisense oligonucleotides inhibits osteosarcoma proliferation and induces apoptosis, potentially via the Fas-mediated pathway.
- Down-regulation of survivin represents a promising therapeutic strategy for osteosarcoma.
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