姜黃素通過線粒體途徑誘導(dǎo)人脈絡(luò)膜黑色素瘤細胞死亡
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本文關(guān)鍵詞: 姜黃素 人脈絡(luò)膜黑色素瘤細胞 細胞色素C caspase-9 caspase-3 出處:《吉林大學(xué)》2010年博士論文 論文類型:學(xué)位論文
【摘要】: 脈絡(luò)膜黑色素瘤(choroidal melanoma, CM)是成人最常見的眼內(nèi)惡性腫瘤。CM的治療方法盡管已有一些新進展,除外科手術(shù)外,目前多采取綜合性治療,如放療、化療、冷凍、激光、免疫及光動力學(xué)等,但其療效有限。目前的研究結(jié)果,尚不足以闡明腫瘤發(fā)生的機制。姜黃素作為天然多酚類物質(zhì)且對多種疾病尤其是癌癥具有抑制和治療作用,因此倍受研究者的關(guān)注。 雖然有實驗表明姜黃素對鼠和人類的皮膚黑色素瘤細胞有毒性作用,但是姜黃素對人眼脈絡(luò)膜黑色素瘤細胞的作用尚無相關(guān)報道。本實驗是通過對人眼脈絡(luò)膜黑色素瘤細胞與成纖維細胞和脈絡(luò)膜黑色素細胞進行比較,研究姜黃素對人眼脈絡(luò)膜黑色素瘤細胞的毒性作用。通過對姜黃素誘導(dǎo)腫瘤細胞產(chǎn)生毒性作用的相關(guān)生物學(xué)機制如線粒體細胞色素c的釋放和caspase-9與caspase-3的激活的研究,進一步闡明姜黃素誘導(dǎo)細胞毒性作用的信號通路。本實驗結(jié)果表明姜黃素能誘導(dǎo)脈絡(luò)膜黑色素瘤細胞死亡且呈劑量依賴效應(yīng)和時間依賴效應(yīng)。姜黃素誘導(dǎo)脈絡(luò)膜黑色素瘤細胞的死亡是通過線粒體細胞色素c的釋放并激活caspase-9-caspase-3通路實現(xiàn)的。 本實驗首次將姜黃素應(yīng)用于人眼脈絡(luò)膜黑色素瘤的研究,這個令人振奮的體外實驗結(jié)果為進一步研究姜黃素對脈絡(luò)膜黑色素瘤的治療奠定了基礎(chǔ),并且隨著姜黃素生物利用率的提高,很可能使這一天然的藥物在將來成為治療脈絡(luò)膜黑色素瘤有效的治療藥物,為脈絡(luò)膜黑色素瘤患者的治療提供一種新方法。
[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.
【學(xué)位授予單位】:吉林大學(xué)
【學(xué)位級別】:博士
【學(xué)位授予年份】:2010
【分類號】:R739.7
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