亚毒性剂量阿霉素提高抗人DR4、 DR5抗体诱导神经胶质瘤细胞凋亡探究.docVIP

亚毒性剂量阿霉素提高抗人DR4、 DR5抗体诱导神经胶质瘤细胞凋亡探究 　 作者：庄国洪, 宋玉国, 毕胜利, 杜柏榕, 朱迅 毕业论文 【关键词】; TNF相关凋亡诱导配体;,死亡受体;,凋亡;,阿霉素 毕业论文 　　Enhancement of glioma cell apoptosis induced by antihuman DR5/DR4 monoclonal antibodies by subtoxic dose of doxorubicin in human 毕业论文 　［Abstract］; AIM: To study the cytotoxic effects of doxorubicin on apoptosis in glioma cell lines U343, U138, U373 induced by antihuman DR4/DR5 monoclonal antibodies (FMU1.4/FMU1.5) and the underlying mechanism. METHODS: Expression of DR4/DR5 was quantitated by flow cytometry. Cytotoxicity exerted by FMU1.4/FMU1.5 on three cell lines was measured by MTT colorimetry and the induced apoptosis was determined by agarose gel electrophoresis. The expression of cytochrome C, FLIP and Ca2+ concentration were also measured. RESULTS: Following the treatment of doxorubicin DR4 and DR5 were highly expressed on the cell surface; The apoptosis of U138 and U373 induced by FMU1.4 and FMU1.5 was stronger. expression of cytochrome C and Ca2+ concentration were enhanced, whereas the expression of FLIP was downregulated. CONCLUSION: Subtoxic doxorubicin applied with antibodies caused higher cell death rate of glioma cells, which may be relevant to DR4/DR5, the release of cytochrome C and FLIP and Ca2+ concentration. 毕业论文 　　[Keywords]TRAIL; death receptor; apoptosis; doxorubicin 毕业论文 　　［摘 要］; 目的: 探讨亚毒性剂量的阿霉素影响抗DR4、 DR5单克隆抗体（mAb） FMU1.4和FMU1.5诱导3株神经胶质瘤细胞株U343 （TRAIL敏感株）、 U138（TRAIL部分敏感株）及U373（TRAIL耐受株）凋亡的作用及可能的机制。方法: 采用流式细胞术检测DR4、 DR5的表达及神经胶质瘤细胞中DNA倍增。用MTT比色法检测mAb FMU1.4和FMU1.5对3株神经胶质瘤细胞增殖的抑制作用。用共聚焦显微镜观察3株细胞中Ca2+ 的浓度。以Western blot检测细胞内色素C、 FLIP[FLICEinhibitory protein, 为一组含有死亡效应结构域（DED）的胞浆蛋白]的表达。结果: 亚毒性剂量的阿霉素作用后, DR5、 DR4在3株细胞中的表达提高; 而mAb FMU1.4、 FMU1.5诱导U138和U373细胞凋亡的作用增强, 细胞内细胞色素C的表达提高, FLIP的表达降低, Ca2+ 浓度增加。结论: 亚毒性剂量的阿霉素与抗DR4、 DR5 mAb联合应用后, 可提高mAb诱导靶细胞凋亡的效应, 其作用机制与DR4、 DR5、 细胞色素C、 FLIP的表达及Ca2+ 的含量有关。 毕业论文 　　［关键词］TNF相关凋亡诱导配体; 死亡受体; 凋亡; 阿霉素 毕业论文 　　死亡受体4、 5 ( death receptor4、 5, DR4、 DR5 )是肿瘤坏死因子相关凋亡诱导配体（TNFrelated apoptosisinduc