高三尖杉酯碱诱导三种肿瘤细胞凋亡的作用机制研究-生物学专业论文.docxVIP

y469327k y469327 k j 7㈠ R姆1 摘要 蓠入实验诞实藤三失杉醒碱能够诱导HL一∞缨照发生凋亡。我们运用稷关 实验证实除了HL=60细胞外，商三尖杉酸碱还能够诱导B16黑色素瘤细胞、 QGY一7703肝癌细胞发生凋亡。分别采用含8000条cDNA的小鼠芯片和含14000 条eDNA的入芯片检测发现，离三尖杉酯碱给药后髓够诱导几百条蒺爵的表达发 生显著变纯，其中已矩有些基因与强亡密甥樱关，有些基因与缨腿周期密切相 关，两有些基因则是掰发现的药物靶旗因；在给药后的不同时间点，表达变化 的基因也不一样。 研究表明，高三尖杉酯碱诱导薏中瘸细胞凋亡的基奉杭馘是TGFB和TNF凋 亡途径被激活，逆转肿瘤巾一些蒸因瓣嚣正常表达交亿。骜物诱导髀癯纲魏凋 亡，势不是襄有的凋亡途经郝披囊动，恧是盛动其中灼一至几条途径。一秘药 物作用于人或小鼠的不同肿瘤细胞，诱导凋亡产生的途径基本一致。凋亡发生 的过稷中，细胞的凋亡与抗凋亡事件自始至终都在发生着。每种细胞抵抗凋亡 的程度不一样，这直接反映在诱导细胞凋亡所需静药物帮蠢土和凋亡出瑗静辩 阗先爱土。淫亡发生嚣孛，有些被激活豹基因愚接凋亡黪，嚣撼裁这些基嚣，本 身就促进了凋亡的发生。细腿凋亡涉及一系列细胞生物学特性的改变，如细胞 周期的变化，耐药性等与药物作用后基因群表达的变化密切相关。(一些新的药 物靶綦因在肿瘤细胞凋亡过程中的具体作精仍需深入研究。‘I l总丽京之，肿瘤缩施蠲亡发生过稷中，一系列缩脆生物学特程也随之渡交， 恧遁避基因芯片发现瓣部分表达蓑异的基因嚣，则可缝是导致纫胞生物特性变 化，并诱发细胞凋亡的关键因素≯6 l蟛 关键词：赢三失杉酯碱：肿瘤细胞；【凋亡；基因表达 AbstractIt Abstract It was reported that homoharringtonine could induce HL一60 cells to apoptosis．We found that homoharringtonine also could induce QGY-7703 ceils and B16 cells to apoptosis．Hundreds of mRNAs were induced during apoptosis after the detection of geneehips．Among these genes studied，some are related to cancer apoptosis，some are related to cell cycle and some are the novel target genes．These genes expressed differently at different time when the cells treated by homoharringtonine underwent apoptosis． Research demonstrated that TGFB and TNF signaling pathways were initiated，which was the main apoptosis mechanism of cancer eelis treated by homoharringtonine．Homoharringtonine also could reverse the abnormal expression of some genes in cells．Not all apoptosis signaling pathways were initiated when cells suffered apoptosis．The apoptosis signaling pathways of human cells and mouse cells was similar when treated by the same drug．The contradiction between apoptosis and resistance to apoptosis existed from beginning to end during apoptosis．The dose of drug and early or late appearance of apoptosis directly reflected the ability that different cells resisted apoptosis．Some genes could resist apoptosis，when these genes were inhibited， apoptosis could happe