Bufalin Inhibits Proliferation and Induces Apoptosis in Osteosarcoma Cells by Downregulating MicroRNA-221.

Bufalin Inhibits Proliferation and Induces Apoptosis in Osteosarcoma Cells by Downregulating MicroRNA-221.
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Bufalin 通过下调 MicroRNA-221 抑制骨肉瘤细胞增殖并诱导细胞凋亡。

DOI:
10.1155/2016/7319464
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发表时间:
2016
期刊:
Evidence-based complementary and alternative medicine : eCAM
影响因子:
--
通讯作者:
Yao Y
Yao Y
中科院分区:
其他
文献类型:
--
作者:
Zhang J;Sha J;Zhou Y;Han K;Wang Y;Su Y;Yin X;Hu H;Yao Y

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蟾蜍灵是中药蟾酥的主要成分,由蟾蜍的皮肤和腮腺毒腺制备而成,对多种恶性肿瘤显示出细胞毒性。在这里,我们报道了蟾蜍灵抑制U-2OS和Saos-2骨肉瘤细胞的增殖并诱导线粒体依赖性细胞凋亡,并产生细胞内活性氧(ROS)。通过microRNA(miR)阵列分析和定量逆转录聚合酶链反应,我们发现用蟾蜍灵治疗后miR-221下调。根据 TargetScan 预测和荧光素酶报告基因检测,Bcl2 结合成分 3 (BBC3) 是 miR-221 的直接靶标。此外,通过 MIMIC 上调 miR-221 并通过小干扰 RNA (siRNA) 抑制 BBC3 可以逆转蟾蜍灵对骨肉瘤细胞的作用。总的来说,我们的数据表明蟾蜍灵通过下调 miR-221 和触发 BBC3 表达来抑制骨肉瘤细胞中的细胞增殖并诱导线粒体依赖性细胞凋亡。
Bufalin, a major component of the Chinese medicine ChanSu, which is prepared from the skin and parotid venom glands of toads, has shown cytotoxicity in several malignant tumors. Here, we reported that bufalin inhibited proliferation and induced mitochondria-dependent apoptosis in U-2OS and Saos-2 osteosarcoma cells with intracellular reactive oxygen species (ROS) production. By microRNA (miR) array analysis and quantitative reverse transcription polymerase chain reaction, we found that miR-221 was downregulated after treatment with bufalin. In accordance with TargetScan prediction and luciferase reporter assay, Bcl2 binding component 3 (BBC3) was the direct target of miR-221. Furthermore, upregulating miR-221 by its MIMIC and suppressing BBC3 by small interfering RNA (siRNA) reversed the effects of bufalin on osteosarcoma cells. Collectively, our data indicate that bufalin inhibits cell proliferation and induces mitochondria-dependent apoptosis in osteosarcoma cells through downregulating miR-221 and triggering BBC3 expression.
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