Oridonin inhibits oral cancer growth and PI3K/Akt signaling pathway
Oridonin inhibits oral cancer growth and PI3K/Akt signaling pathway
复制标题
冬凌草甲素抑制口腔癌生长和 PI3K/Akt 信号通路
DOI：
10.1016/j.biopha.2018.02.011
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发表时间：
2018-04-01
影响因子：
7.5
通讯作者：
Xia, Juan
中科院分区：
文献类型：
--
作者：
Yang, Jing;Ren, Xianyue;Xia, Juan
冬凌草甲素是从冬凌草中提取的一种具有生物活性的二萜类化合物，已被证明对多种癌症具有抗癌作用。然而，其对口腔鳞状细胞癌（OSCC）细胞的影响尚不清楚。本研究旨在利用OSCC细胞系UM 1和SCC 25研究冬凌草甲素对OSCC细胞的抗癌能力，包括增殖、凋亡及其相关机制。结果表明，冬凌草甲素不仅能抑制UM 1和SCC 25细胞的增殖和克隆形成，而且能诱导细胞周期阻滞于G2/M期，并呈剂量依赖性地诱导细胞凋亡。Western blot结果显示，冬凌草甲素处理后Bax/Bcl-2比值增加，caspase-3、caspase-9和PARP-1的裂解激活。冬凌草甲素还可通过下调细胞周期蛋白cyclin B1或上调细胞周期蛋白cyclin D1、cyclin D3、P21、p-CDK 1和cyclin A2等G2/M期转换相关蛋白的表达，诱导OSCC细胞发生G2/M期阻滞。另外，冬凌草甲素治疗能显著抑制PI 3 K和Akt的磷酸化，抑制OSCC裸鼠移植瘤的生长。以上结果提示，冬凌草甲素可能通过抑制PI 3 K/Akt信号通路，诱导细胞凋亡和G2/M期阻滞而发挥抗口腔癌作用。因此，冬凌草甲素可能是一种潜在的治疗口腔癌的抗癌药物。
Oridonin, a bioactive diterpenoid purified from Rabdosia rubescens, has been shown to possess anticancer capacity in several cancer types. However, its effects on oral squamous cell carcinoma (OSCC) cells remain unclear. This study aimed to investigate the anticancer ability of oridonin in OSCC cells, including proliferation, apoptosis and underlying mechanisms using the OSCC cell lines, UM1 and SCC25. The results showed that oridonin not only inhibited proliferation and clonal formation but also induced G2/M cell cycle arrest and apoptosis in UM1 and SCC25 cells in a dose-dependent manner. Western blot revealed that oridonin treatment increased the ratio of Bax/Bcl-2, and activated the cleavage of caspase-3, caspase-9 and PARP-1. Oridonin also induced G2/M phase arrest in OSCC cells via down-regulating the G2/M transition-related proteins such as cyclin B1 or upregulating cyclin D1, cyclin D3, P21, p-CDK1 and cyclin A2. In addition, oridonin treatment significantly inhibited the phosphorylation of PI3K and Akt and inhibited tumor growth of OSCC xenograft in nude mice. Taken together, these results suggested that oridonin possesses anti-oral cancer capacity via inhibiting the PI3K/Akt signaling and induce apoptosis and G2/M-phase arrest. Therefore, oridonin may be a potential anticancer drug for the treatment of oral cancer.