【作者】 王菁；

【导师】 陈建忠；

【作者基本信息】 浙江大学 ， 免疫学， 2018， 硕士

【摘要】 大量用于医学诊治的放射性药物能发射β射线,诱导细胞凋亡,但是其机制仍不明确。本研究的目的是研究锶89(89Sr)诱导人乳腺癌MCF-7细胞株的凋亡及其分子机制。研究用不同放射性浓度的89Sr处理乳腺癌MCF-7细胞株,采用MTT比色法、流式细胞术和免疫组化等方法检测细胞增殖能力、细胞周期、细胞凋亡、线粒体膜电位变化、Fas基因表达及P53和Bcl-2蛋白表达情况。结果发现,不同放射性浓度的89Sr照射能显著抑制MCF-7细胞的增殖,细胞周期在G2-M期阻滞明显,而且MCF-7细胞增殖能力下降和细胞周期阻滞与89Sr处理浓度呈现浓度依赖。89Sr照射后线粒体膜电位的降低、细胞凋亡明显增强,凋亡率最高达到46.28%,同时Fas受体和P53表达升高,而bcl-2表达下降。研究表明在一定范围的放射性浓度照射能诱导MCF-7细胞凋亡,其机制可能与其调节Fas受体、P53和Bcl-2等凋亡相关分子的表达有关。我们的研究为肿瘤放射治疗提供了理论依据。更多还原

【Abstract】 Many radiopharmaceuticals used for medical diagnosis and therapy are beta emitters;however,the mechanism of the cell death caused by beta-irradiation is not well understood.The objective of this study is to investigate the apoptosis of human breast carcinoma MCF-7 cell lines induced by Strontium-89(89Sr)and its underlying mechanism.High-metastatic breast cancer cells MCF-7 were treated with l9Sr at different radioactive concentrations.The inhibition rate of cell proliferation was measured by MTT assay.The cell cycle retardation,cell apoptosis,mitochondrion transmembrane potential change,and Fas receptor expression were detected by FACS.The protein expressions of pro-apoptotic P53 and anti-apoptotic Bcl-2 were analyzed by immunohistochemistry.When the MCF-7 cells were treated with various concentrations of 89Sr,the cell proliferation was significantly inhibited and the cell cycle was mainly retarded in G2-M phase in a dose-dependent manner.In addition,the mitochondrial transmembrane potential was decreased and the apoptosis of MCF-7 cells was observed after the MCF-7 cells were treated with 89Sr.The apoptotic rate was up to 46.28%.The expressions of Fas receptor and pro-apoptotic P53 were increased,while the expression of anti-apoptotic Bcl-2 was decreased.These findings indicated that 89Sr may induce the apoptosis of MCF-7 by regulation the expression of Fas receptor,P53 and Bcl-2.Our study providetherapeutic evidence for tumor radiotherapy.更多还原