Taurine exhibits an apoptosis-inducing effect on human nasopharyngeal carcinoma cells through PTEN/Akt pathways in vitro
Taurine exhibits an apoptosis-inducing effect on human nasopharyngeal carcinoma cells through PTEN/Akt pathways in vitro
复制标题
DOI：
10.1007/s00726-018-2651-2
复制
发表时间：
2018-12-01
期刊：
影响因子：
3.5
通讯作者：
Murata, Mariko
中科院分区：
文献类型：
--
作者：
He, Feng;Ma, Ning;Murata, Mariko
鼻咽癌（Nasopharyngeal carcinoma，NPC）是我国南方地区的一种常见的头颈部恶性肿瘤。已有研究证实牛磺酸通过抑制细胞增殖和诱导细胞凋亡对多种人类肿瘤具有抗癌作用。然而，其抗鼻咽癌作用的分子机制尚不清楚。为了阐明这些抗癌机制，我们进行了细胞活力和集落形成测定。通过流式细胞术定量凋亡细胞。Western blot检测细胞凋亡相关蛋白的表达水平。结果表明，牛磺酸对鼻咽癌细胞的增殖有明显的抑制作用，而对永生化的正常鼻咽细胞系的抑制作用则很弱。牛磺酸以剂量依赖方式抑制鼻咽癌细胞系的集落形成并诱导其凋亡。此外，牛磺酸以剂量依赖性方式增加caspase-9/3的活性形式。牛磺酸下调了抗凋亡蛋白Bcl-xL，上调了促凋亡蛋白Bax和GRP 78（一种主要的内质网（ER）伴侣）。这些结果表明，线粒体和ER应激信号参与细胞凋亡。此外，牛磺酸增加了PTEN（10号染色体上缺失的磷酸酶和张力蛋白同源物）和p53的水平，并减少了磷酸化Akt（蛋白激酶B）。结论：牛磺酸可能通过激活PTEN并同时失活Akt，抑制鼻咽癌细胞增殖并诱导细胞凋亡。
Nasopharyngeal carcinoma (NPC) is a distinctive type of head and neck malignancy with a high incidence in southern China. Previous studies have confirmed that taurine shows an anti-cancer effect on a variety of human tumors by inhibiting cell proliferation and inducing apoptosis. However, the underlying molecular mechanism of its anti-cancer effect on NPC is not well understood. To clarify these anti-cancer mechanisms, we performed cell viability and colony formation assays. Apoptotic cells were quantified by flow cytometry. The expression levels of apoptosis-related proteins were evaluated by Western blot. The results showed that taurine markedly inhibited cell proliferation in NPC cells, but only slightly in an immortalized normal nasopharyngeal cell line. Taurine suppressed colony formation and induced apoptosis of NPC cell lines in a dose-dependent manner. Furthermore, taurine increased the active form of caspase-9/3 in a dose-dependent manner. Taurine down-regulated the anti-apoptotic protein Bcl-xL and up-regulated the pro-apoptotic protein Bax and GRP78, a major endoplasmic reticulum (ER) chaperone. These results suggest the involvement of mitochondrial and ER stress signaling in apoptosis. In addition, taurine increased the levels of PTEN (phosphatase and tensin homolog deleted on chromosome 10) and p53, and reduced phosphorylated Akt (protein kinase B). In conclusion, taurine may inhibit cell proliferation and induce apoptosis in NPC through PTEN activation with concomitant Akt inactivation.