Zhang Jianjun, Sha Jingjing, Zhou Yan, Han Kun, Wang Yaling, Su Yang, Yin Xiuyi, Hu Haiyan, Yao Yang
Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Jin Yang Community Health Service Center, Shanghai 200136, China.
Evid Based Complement Alternat Med. 2016;2016:7319464. doi: 10.1155/2016/7319464. Epub 2016 Dec 15.
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.
蟾酥灵是中药蟾酥的主要成分，蟾酥由蟾蜍的皮肤和腮腺毒液腺制成，已在多种恶性肿瘤中显示出细胞毒性。在此，我们报告蟾酥灵通过产生细胞内活性氧（ROS）抑制U-2OS和Saos-2骨肉瘤细胞的增殖并诱导线粒体依赖性凋亡。通过微小RNA（miR）阵列分析和定量逆转录聚合酶链反应，我们发现用蟾酥灵处理后miR-221表达下调。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，通过其模拟物上调miR-221并通过小干扰RNA（siRNA）抑制BBC3可逆转蟾酥灵对骨肉瘤细胞的作用。总体而言，我们的数据表明蟾酥灵通过下调miR-221并触发BBC3表达来抑制骨肉瘤细胞的增殖并诱导线粒体依赖性凋亡。
