Calpeptin Prevents Malignant Pleural Mesothelioma Cell Proliferation via the Angiopoietin1/Tie2 System.
Calpeptin Prevents Malignant Pleural Mesothelioma Cell Proliferation via the Angiopoietin1/Tie2 System.
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发表时间：
2016-07
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通讯作者：
C. Tabata;R. Tabata;T. Nakano
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作者：
C. Tabata;R. Tabata;T. Nakano
恶性胸膜间皮瘤(MPM)是一种与石棉暴露相关的间皮源性侵袭性恶性肿瘤，对常规化疗和放射治疗反应有限。因此，MPM患者的总体生存状况仍然很差。MPM治疗策略的开发进展有限。我们最近报道了钙蛋白酶抑制剂，即钙肽蛋白，通过抑制肺成纤维细胞的增殖而抑制肺纤维化的发生。在本研究中，我们检测了钙肽蛋白对MPM细胞生长的预防作用，MPM起源于间充质细胞，类似于肺成纤维细胞。CalPeptin可抑制MPM细胞的增殖，但不能抑制间皮细胞的增殖。抑制血管生成素(Ang)1和Tie2mRNA在MPM细胞中的表达，但不抑制间皮细胞的表达；2)通过NFkB依赖途径抑制Ang1诱导的MPM细胞的增殖，这可能是其抑制MPM细胞生长的机制之一。这些结果提示钙肽可能用于MPM的临床治疗。
Malignant pleural mesothelioma (MPM), an aggressive malignant tumor of mesothelial origin associated with asbestos exposure, shows a limited response to conventional chemotherapy and radiotherapy. Therefore, the overall survival of MPM patients remains very poor. Progress in the development of therapeutic strategies for MPM has been limited. We recently reported that the calpain inhibitor, calpeptin exerted inhibitory effects on pulmonary fibrosis by inhibiting the proliferation of lung fibroblasts. In the present study, we examined the preventive effects of calpeptin on the cell growth of MPM, the origin of which is mesenchymal cells, similar to lung fibroblasts. Calpeptin inhibited the proliferation of MPM cells, but not mesothelial cells. It also prevented 1) the expression of angiopoietin (Ang)1 and Tie2 mRNA in MPM cells, but not mesothelial cells and 2) the Ang1induced proliferation of MPM cells through an NFkB dependent pathway, which may be the mechanism underlying the preventive effects of calpeptin on the growth of MPM cells. These results suggest potential clinical use of calpeptin for the treatment of MPM.