Apoptosis of human non-small-cell lung cancer A549 cells triggered by evodiamine through MTDH-dependent signaling pathway
Apoptosis of human non-small-cell lung cancer A549 cells triggered by evodiamine through MTDH-dependent signaling pathway
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DOI：
10.1007/s13277-015-3174-z
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发表时间：
2015-02
期刊：
影响因子：
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通讯作者：
Y. Zou;Xi-hu Qin;H. Xiong;Feng Zhu;Tao Chen;Hong-ge Wu
中科院分区：
文献类型：
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作者：
Y. Zou;Xi-hu Qin;H. Xiong;Feng Zhu;Tao Chen;Hong-ge Wu
Metadherin（MTDH）是一种新的癌蛋白，在肿瘤的发生、发展过程中起着重要作用。MTDH的过表达促进肺癌细胞的存活和增殖。可以抑制MTDH活化的试剂将具有开发用于癌症治疗的潜力。本研究探讨了吴茱萸碱对人非小细胞肺癌A549细胞的抗肿瘤作用及其对MTDH通路的抑制作用。3-（4，5-二甲基-噻唑-2-基）-2，5-二苯基四氮唑溴化盐（MTT）和Annexin V/PI染色结果表明，吴茱萸碱和MTDH短发夹RNA（shRNA）通过诱导细胞凋亡抑制A549细胞的增殖。此外，吴茱萸碱或MTDH shRNA在相同条件下诱导A549细胞中caspase-3的活化。此外，Western blotting分析显示，吴茱萸碱或MTDH shRNA处理A549细胞导致促凋亡蛋白Bax表达增加，但抗凋亡蛋白Bcl-2和MTDH的表达水平降低，这两者共同解释了凋亡性细胞死亡。总之，我们的结果表明，吴茱萸碱抑制肺癌细胞的增殖，至少，部分地通过抑制MTDH表达和激活凋亡。
Metadherin (MTDH), a novel oncoprotein, has been implicated in the carcinogenesis in various aspects of tumor malignancy. Overexpression of the MTDH promotes the survival and proliferation of lung cancer cells. Agent that can suppress MTDH activation would have potential to be developed for cancer therapeutics. In this study, we investigated the antitumor effect of evodiamine in human non-small-cell lung carcinoma (NSCLC) A549 cell line and the inhibitory effect of evodiamine on MTDH pathway. 3-(4,5-Dimethyl- thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and annexin V/propidium iodide (PI) staining assays demonstrated that evodiamine or MTDH short hairpin RNA (shRNA) significantly inhibited proliferation of A549 cells via induction of apoptosis. Besides, evodiamine or MTDH shRNA-induced activation of the caspase-3 in A549 cells under same conditions. In addition, Western blotting analysis showed that treatment of A549 cells with evodiamine or MTDH shRNA resulted in an increase of proapoptotic protein Bax expression but decreased the expression levels of antiapoptotic protein Bcl-2 and MTDH, which altogether account for apoptotic cell death. Taken together, our results suggest that the evodiamine suppress the proliferation of lung cancer cells, at least, in part, via inhibition of MTDH expression and activation of apoptosis.