Baicalin Induces Apoptotic Death of Human Chondrosarcoma Cells through Mitochondrial Dysfunction and Downregulation of the PI3K/Akt/mTOR Pathway
Baicalin Induces Apoptotic Death of Human Chondrosarcoma Cells through Mitochondrial Dysfunction and Downregulation of the PI3K/Akt/mTOR Pathway
复制标题
黄芩苷通过线粒体功能障碍和 PI3K/Akt/mTOR 通路下调诱导人软骨肉瘤细胞凋亡
DOI：
10.1055/a-0791-1049
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发表时间：
2019-03-01
期刊：
影响因子：
2.7
通讯作者：
Teng, Honglin
中科院分区：
文献类型：
--
作者：
Zhu, Minyu;Ying, Jinwei;Teng, Honglin
摘要本研究旨在探讨黄芩苷对人软骨肉瘤的细胞毒作用及体外抗肿瘤作用。我们研究了黄芩苷对人软骨肉瘤细胞生长和凋亡的影响。黄芩苷对SW 1353和CH 2879细胞的生长有明显的抑制作用，且呈剂量和时间依赖性，但对正常软骨细胞的生长无明显抑制作用。黄芩苷在SW 1353移植的裸鼠中减少肿瘤生长并诱导凋亡死亡，而不降低其体重。进一步研究表明黄芩苷降低线粒体膜电位，上调Bax和细胞色素c的表达，下调Bcl-2和线粒体细胞色素的表达，激活caspase-3和caspase-9。黄芩苷在体内和体外均通过降低磷酸化肌醇3-激酶、磷酸化蛋白激酶B和磷酸化哺乳动物雷帕霉素靶蛋白的表达来抑制磷酸肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白通路。此外，与接受黄芩苷的小鼠相比，接受SC 79和黄芩苷的小鼠表现出更大的肿瘤大小。与接受黄芩苷的小鼠相比，接受LY 294002和黄芩苷的小鼠显示出较小的肿瘤大小。在体外研究中，SC 79和LY 294002以相同的方式影响黄芩苷诱导的对软骨肉瘤细胞的细胞毒性作用。我们的数据表明黄芩苷通过诱导细胞凋亡和抑制磷酸肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶点途径对人软骨肉瘤具有治疗效果。黄芩苷可被认为是一种潜在的治疗软骨肉瘤的药物。
Abstract The aim of the present study was to investigate the cytotoxic and antitumour effects of baicalin in human chondrosarcoma both in vivo and in vitro. We examined the effects of baicalin on the growth and apoptosis of human chondrosarcoma cells. Baicalin inhibited the growth of SW1353 and CH2879 cells in a dose- and time-dependent manner, but did not inhibit the growth of normal chondrocytes. Baicalin reduced tumour growth and induced apoptotic death in SW1353-transplanted nude mice without reducing their body weight. Further studies showed that baicalin reduced the mitochondrial membrane potential, upregulated the expression of Bax and cytoplasmic cytochrome c, downregulated the expression of Bcl-2 and mitochondrial cytochromes, and activated caspase-3 and caspase-9. Baicalin inhibited the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathway by decreasing the expression of phosphorylated phosphoinositide 3-kinase, phosphorylated protein kinase B, and phosphorylated mammalian target of rapamycin both in vivo and in vitro. Moreover, the mice that received SC79 and baicalin exhibited a greater tumour size compared with the mice that received baicalin. The mice that received LY294002 and baicalin showed a smaller tumour size compared with the mice that received baicalin. In the in vitro study, SC79 and LY294002 affected the baicalin-induced cytotoxic effects on chondrosarcoma cells in the same manner. Our data suggest baicalin has therapeutic efficacy in human chondrosarcoma through the induction of apoptosis and inhibition of the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathway. Baicalin can be considered a potential therapeutic agent for treating chondrosarcomas.