Swainsonine promotes apoptosis in human oesophageal squamous cell carcinoma cells in vitro and in vivo through activation of mitochondrial pathway
Swainsonine promotes apoptosis in human oesophageal squamous cell carcinoma cells in vitro and in vivo through activation of mitochondrial pathway
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苦马豆素通过激活线粒体途径在体外和体内促进人食管鳞状细胞癌细胞凋亡
DOI：
10.1007/s12038-012-9265-8
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发表时间：
2012-12-01
影响因子：
2.9
通讯作者：
Tong, Dewen
中科院分区：
文献类型：
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作者：
Li, Zhaocai;Huang, Yong;Tong, Dewen
Swainsonine是一种天然吲哚吡啶类生物碱，具有抗肿瘤作用，可诱导人胃癌和肺癌细胞凋亡。在本研究中，我们评估了苦马豆素对几种食管鳞状细胞癌细胞的抗肿瘤作用，并探讨了相关的分子机制。MTT法检测，马豆素处理对Eca-109、TE-1和TE-10细胞的生长呈浓度依赖性。形态学观察、DNA阶梯检测和流式细胞术分析表明，马豆素处理可诱导Eca-109细胞体外凋亡。进一步结果表明，马豆素处理可上调Bax，下调Bcl-2表达，触发Bax向线粒体易位，破坏线粒体完整性，激活线粒体介导的凋亡通路，随后细胞色素c释放，激活caspase-9和caspase-3，促进PARP的裂解，导致Eca-109细胞凋亡。此外，马豆素处理抑制Bcl-2表达，促进Bax易位、细胞色素c释放和caspase-3在异种移植肿瘤细胞中的激活，导致马豆素处理的异种移植小鼠组肿瘤体积和肿瘤重量较对照组显著减小。综上所述，本研究表明，苦马豆素通过激活线粒体介导的caspase依赖途径抑制Eca-109细胞的生长。
Swainsonine, a natural indolizidine alkaloid, has been reported to have antitumour effects, and can induce apoptosis in human gastric and lung cancer cells. In the present study, we evaluated the antitumour effects of swainsonine on several oesophageal squamous cell carcinoma cells and investigated relative molecular mechanisms. Swainsonine treatment inhibited the growth of Eca-109, TE-1 and TE-10 cells in a concentration-dependent manner as measured by MTT assay. Morphological observation, DNA laddering detection and flow cytometry analysis demonstrated that swainsonine treatment induced Eca-109 cell apoptosis in vitro. Further results showed that swainsonine treatment up-regulated Bax, down-regulated Bcl-2 expression, triggered Bax translocation to mitochondria, destructed mitochondria integrity and activated mitochondria-mediated apoptotic pathway, followed by the release of cytochrome c, which in turn activated caspase-9 and caspase-3, promoted the cleavage of PARP, resulting in Eca-109 cell apoptosis. Moreover, swainsonine treatment inhibited Bcl-2 expression, promoted Bax translocation, cytochrome c release and caspase-3 activation in xenograft tumour cells, resulting in a significant decrease of tumour volume and tumour weight in the swainsonine-treated xenograft mice groups compared with that in the control group. Taken together, this study demonstrated that swainsonine inhibited Eca-109 cells growth through activation of mitochondria-mediated caspase-dependent pathway.