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新型線粒體靶向鉑類配合物Mor-platin抑制肝癌細胞HepG2增殖和抑制細胞球侵襲的研究

發(fā)布時間:2018-08-11 15:56
【摘要】:目的:探討新型線粒體靶向性鉑類配合物Mor-platin對人肝癌細胞HepG2的細胞增殖和細胞球侵襲的影響。方法:運用細胞毒性實驗CCK-8法,比較新型線粒體靶向性鉑類配合物Mor-platin和經典鉑類抗癌藥順鉑(cisplatin)對人肝癌細胞HepG2的細胞增殖抑制作用;利用激光共聚焦顯微鏡觀察Mor-platin是否靶向于線粒體;利用透射電子顯微鏡觀察Mor-platin對細胞線粒體形態(tài)的影響;流式細胞儀檢測Mor-platin作用細胞后細胞凋亡的改變;建立三維腫瘤細胞球模型,探討Mor-platin對細胞球侵襲的影響。結果:Mor-platin能夠抑制HepG2細胞增殖,半數抑制濃度(IC_(50))少于cisplatin;Mor-platin能夠靶向到線粒體;加Mor-platin后,細胞線粒體膜結構不完整,嵴不清晰或消失以及線粒體中有大片空白區(qū)域;Mor-platin引起的細胞凋亡具有劑量依賴性;三維腫瘤細胞球模型顯示,Mor-platin處理的細胞球面積小于對照組。結論:新型線粒體靶向性鉑配合物Mor-platin能夠靶向于細胞的線粒體,引起線粒體形態(tài)變化,抑制細胞增殖,最終導致細胞凋亡,Mor-platin還能抑制三維腫瘤細胞球侵襲,比cisplatin具有更好的抗癌效果。上述研究結果提示Mor-platin具有成為新抗腫瘤藥物的潛質。
[Abstract]:Aim: to investigate the effects of a novel mitochondrial targeted platinum complex (Mor-platin) on the proliferation and cell ball invasion of human hepatoma cell line HepG2. Methods: cytotoxicity assay (CCK-8) was used to compare the inhibitory effects of a novel mitochondrial targeted platinum complex (Mor-platin) and a classical platinum anticancer agent (cisplatin (cisplatin) on the proliferation of human hepatoma cell line HepG2. Laser confocal microscopy was used to observe whether Mor-platin was targeted on mitochondria, transmission electron microscope was used to observe the effect of Mor-platin on the morphology of mitochondria, flow cytometry was used to detect the changes of cell apoptosis after Mor-platin treatment. Three-dimensional tumor cell ball model was established to investigate the effect of Mor-platin on cell ball invasion. Results the proliferation of HepG2 cells was inhibited by the addition of Mor-platin, and the half inhibitory concentration (IC50) was less than that of cisplatin Mor-platin targeting mitochondria, and the membrane structure of mitochondria was incomplete after addition of Mor-platin. The apoptosis induced by Mor-platin in mitochondria was dose-dependent, and the area of cells treated with Mor-platin was smaller than that of control group. Conclusion: Mor-platin, a novel mitochondrial targeted platinum complex, can target the mitochondria, induce mitochondrial morphological changes, inhibit cell proliferation, and eventually lead to apoptosis. Mor-platin can also inhibit the invasion of three-dimensional tumor cells. It has better anti-cancer effect than cisplatin. These results suggest that Mor-platin has the potential to be a new anti-tumor drug.
【作者單位】: 桂林醫(yī)學院附屬醫(yī)院肝膽胰外科;蘇州大學附屬兒童醫(yī)院病案統(tǒng)計室;
【基金】:國家自然科學基金項目(編號:81372163) 廣西省自然科學基金項目(編號:2015GXNSFAA139111)資助~~
【分類號】:R730.5

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相關博士學位論文 前2條

1 許德晨;鉑類配合物的抗癌作用機理的研究[D];中國科學技術大學;2014年

2 張金超;新型鉑(Ⅱ)類配合物的合成、表征和抗腫瘤活性的研究[D];浙江大學;2000年

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