Department of Orthopaedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.
Neoplasma. 2010;57(6):501-6. doi: 10.4149/neo_2010_06_501.
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.
osteosarcoma, Survivin, apoptosis, Fas.
Survivin 可能在骨肉瘤的发生发展中起重要作用。本研究选择高表达 Survivin 的骨肉瘤细胞系 MG-63，观察反义寡核苷酸对 Survivin 的靶向作用对凋亡诱导和增殖抑制的影响。结果显示，用 MTT 和流式细胞术方法检测，Survivin 阳性细胞 MG-63 的凋亡率和增殖抑制率明显增加。我们发现生长抑制率和凋亡率呈剂量依赖性变化。当反 Survivin 寡核苷酸浓度为 600 nM 时，作用达到高峰。用 RT-PCR 和 Western-blot 方法检测 MG-63 中 Survivin 的 mRNA 和蛋白表达。我们观察到，当转染浓度为 200 nM、400 nM 和 600 nM 的反 Survivin 寡核苷酸时，Survivin 的 mRNA 和蛋白表达降低。同时，我们发现随着反 Survivin 寡核苷酸浓度从 200 nM 增加到 600 nM，Fas 的 mRNA 和蛋白表达上调，与 Survivin 的表达变化呈负相关。这些数据表明 Survivin 可能在骨肉瘤的发生发展中起重要作用，用反 Survivin 寡核苷酸阻断 Survivin 可通过降低 Survivin 的表达抑制骨肉瘤的增殖并诱导其凋亡，激活 Fas 介导的凋亡。反义寡核苷酸下调 Survivin 可能是骨肉瘤治疗的有效策略，并可能提高治疗效果。
骨肉瘤，Survivin，凋亡，Fas。
