姜黄素通过线粒体途径诱导人脉络膜黑色素瘤细胞死亡

发布时间：2018-03-01 00:16

本文关键词： 姜黄素人脉络膜黑色素瘤细胞细胞色素C caspase-9 caspase-3　出处：《吉林大学》2010年博士论文　论文类型：学位论文

【摘要】： 脉络膜黑色素瘤(choroidal melanoma, CM)是成人最常见的眼内恶性肿瘤。CM的治疗方法尽管已有一些新进展,除外科手术外,目前多采取综合性治疗,如放疗、化疗、冷冻、激光、免疫及光动力学等,但其疗效有限。目前的研究结果,尚不足以阐明肿瘤发生的机制。姜黄素作为天然多酚类物质且对多种疾病尤其是癌症具有抑制和治疗作用,因此倍受研究者的关注。虽然有实验表明姜黄素对鼠和人类的皮肤黑色素瘤细胞有毒性作用,但是姜黄素对人眼脉络膜黑色素瘤细胞的作用尚无相关报道。本实验是通过对人眼脉络膜黑色素瘤细胞与成纤维细胞和脉络膜黑色素细胞进行比较,研究姜黄素对人眼脉络膜黑色素瘤细胞的毒性作用。通过对姜黄素诱导肿瘤细胞产生毒性作用的相关生物学机制如线粒体细胞色素c的释放和caspase-9与caspase-3的激活的研究,进一步阐明姜黄素诱导细胞毒性作用的信号通路。本实验结果表明姜黄素能诱导脉络膜黑色素瘤细胞死亡且呈剂量依赖效应和时间依赖效应。姜黄素诱导脉络膜黑色素瘤细胞的死亡是通过线粒体细胞色素c的释放并激活caspase-9-caspase-3通路实现的。本实验首次将姜黄素应用于人眼脉络膜黑色素瘤的研究,这个令人振奋的体外实验结果为进一步研究姜黄素对脉络膜黑色素瘤的治疗奠定了基础,并且随着姜黄素生物利用率的提高,很可能使这一天然的药物在将来成为治疗脉络膜黑色素瘤有效的治疗药物,为脉络膜黑色素瘤患者的治疗提供一种新方法。
[Abstract]:Choroidal melanoma (CMM) is the most common treatment for intraocular malignant tumors in adults. The present research results are not enough to elucidate the mechanism of tumorigenesis. Curcumin, as a natural polyphenols, has inhibitory and therapeutic effects on many diseases, especially cancer. Therefore, researchers pay close attention to it. Although experiments have shown that curcumin has toxic effects on mouse and human skin melanoma cells, However, the effect of curcumin on human choroidal melanoma cells has not been reported. In this study, human choroidal melanoma cells were compared with fibroblasts and choroidal melanocytes. To study the toxic effect of curcumin on human choroidal melanoma cells. The biological mechanisms of curcumin induced cytotoxicity such as mitochondrial cytochrome c release and activation of caspase-9 and caspase-3 were studied. The results show that curcumin can induce the death of choroidal melanoma cells in a dose-dependent and time-dependent manner. Melanoma cell death is achieved through the release of mitochondrial cytochrome c and activation of the caspase-9-caspase-3 pathway. Curcumin was applied to the study of human choroidal melanoma for the first time. This exciting experimental result laid a foundation for further study on the treatment of choroidal melanoma by curcumin. With the increase of the bioavailability of curcumin, this natural drug may become an effective treatment for choroidal melanoma in the future, and provide a new method for the treatment of choroidal melanoma.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2010
【分类号】：R739.7

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