【作者】 李秋娟；

【导师】 仲来福；

【作者基本信息】 大连医科大学 ， 生物化学与分子生物学， 2005， 硕士

【摘要】 前言维生素E琥珀酸酯(RRR-Tocopheryl Succinate,Vitamin E Succinate, VES)是天然维生素E中活性最强的一种同型衍生物。国内外研究表明,VES在体内和体外均可有效地抑制多种肿瘤细胞生长,如对胃癌、乳腺癌、前列腺癌、结肠癌等肿瘤细胞。尽管VES作用机制尚不十分清楚,迄今研究业已发现VES可将肿瘤细胞周期阻滞在G1期,促进肿瘤细胞分化,抑制肿瘤细胞DNA合成及诱导肿瘤细胞凋亡。有研究认为,VES在诱导胃癌细胞凋亡过程中启动了Fas信号转导途径,VES启动Fas后,Fas相关蛋白(FADD)和天冬氨酸特异性半胱氨酸蛋白酶(caspase-8)联结起来,活化caspase级联反应,从而启动了Fas/FADD/ caspase-8的凋亡信号途径。值得注意的是,VES并不抑制正常分裂细胞的生长。化疗药物通常没有这种选择性。顺铂(cisplatin,CP)是迄今常用的抗肿瘤药物之一。临床上在头颈部癌、睾丸癌、卵巢癌等多种肿瘤化疗中,CP常被列为首选药物,或与其它药物合用,增强抗肿瘤作用。CP毒副作用也不容忽视,其肝肾毒性、骨髓毒性等是十分严重的,这就限制了CP在化疗中的使用剂量,从而影响疗效。寻求有效的防护剂一直是CP毒理学研究的热点。本文旨在研究VES对CP肝细胞毒性的影响,并探讨VES与CP合用增强抗肿瘤细胞增殖作用的可能机制。方法将分离的人和大鼠肝细胞,接种于胶原铺被的96孔板,细胞贴壁后,分别加入一系列浓度的CP、VES及CP+VES,于48h后用噻唑蓝(MTT)比色法检测细胞存活率,并计算半数抑制浓度(IC50)。MTT法检测CP、VES及CP+VES对人前列腺癌细胞系DU-145和人大更多还原

【Abstract】 Introduction: Vitamin E Succinate(VES) is the most active derivatives of Vitamin E. Early reports show that VES effectively inhibits the growth of several cancer cells in vivo and in vitro, such as human gastric adenocarcinoma cell, human breast cancer cell line, human prostate cancer cell, human colon cancer cell line and so on. Although the exact mechanisms remain largely unclear, previous studies suggeste that VES arreste the cycle of cancer cells at G1, promotes the proliferation, inhibites DNA synthesis and induces apoptosis. Some reports show that after VES triggeres Fas singaling system, the combining of FADD and caspase-8 activates, caspase linked responses, and there by the apoptosis singaling system was started. It is noted that VES does not inhibit proliferating of normal cells, but chemotherapeutic drugs has not this selectivity. Cisplatin(CP), a commonly used anticarcinomo drug, is the chief chemotherapeutic agent in clinical treatment of cancers, including the head, neck, testis and ovary. Unfortunately, it has been found that there are many side effects for this medicine, such as bone marrow suppression, hepatotoxicity and nephrotoxicity, and these side effects limite the dose of CP and its curative effect. At present, there is much more to ameliorate toxicity. In this study, we investigated the effects of VES on CP-induced hepatocyte cytotoxicity and the plausible mechanisms of combination of VES and CP.Method: Human and rat hepatocytes isolated were inoculated to 96-well collagen-coated plate. After cell attachment, different concentration solution of CP, VES and CP+VES were added to each well and incubation更多还原