紫杉醇抗肿瘤的分子机制

Antitumor mechanism of taxinol

目的:近年来,国内外的研究人员从不同角度对植物提取药紫杉醇的抗癌机制等方面进行了诸多研究,发现紫杉醇对多种癌细胞具有显著的疗效,对其机制的认识有助于更好的临床应用。资料来源:本文应用计算机检索Medline数据库1979-01/2006-2期间的相关文章,检索词“Chemotherapy,tumor,taxinol”,限定文章语言种类为英文。资料选择:选取紫杉醇机制研究和临床应用相关文献。纳入标准:①随机对照研究。②基础或临床研究包含平行对照组研究。排除标准:重复性研究或综述类文章。资料提炼:对资料进行初审,共收集到58篇关于紫杉醇与抗肿瘤的机制研究文献。20篇为随机对照研究,且基础或临床研究包含平行对照组研究,符合纳入标准;排除38篇为重复性研究或综述类文章。资料综合:①紫杉醇作为广谱抗癌药,对普通抗癌药物耐药的某些晚期肿瘤有良好的疗效,并且对于多种临床恶性肿瘤疗效显著而用于临床。近年的实验结果表明,紫杉醇对卡伯肉瘤细胞有显著的细胞毒作用,对P388、P1534白血病有很高的活性,能抑制W256肉瘤、S180和肺癌的生长。②紫杉醇抗肿瘤可能通过调控微管动力学稳定机制,诱导细胞凋亡机制,调控免疫机制起作用。③一般认为紫杉醇的主要靶位点是微管蛋白/微管系统,它能促进微管聚合,抑制微管降解,使细胞分裂阻滞在G2/M期,能够诱导多种癌细胞的凋亡,而大量研究表明紫杉醇对微管系统的作用及对G2/M期的阻滞并不是诱导细胞凋亡的唯一机制。④紫杉醇其药理作用新颖在于通过抑制微管蛋白和组成微管的微管蛋白二聚体动态平衡来诱导肿瘤细胞凋亡。结论:①紫杉醇被认为是一种广谱抗癌药物,联合其他常用抗肿瘤药物,疗效可进一步提高,成为继环磷酰胺、阿霉素之后又一重要抗肿瘤药物。②可能有许多信号传导通路和机制参与紫杉醇诱导肿瘤细胞的凋亡。

OBJECTIVE： Recently, many oversea and domestic researchers have carried out the various researches to study the anticancer mechanisms of taxinol extracted from plants, and reveal that taxinol has significant therapeutic effects on many cancer ceils, which may conduce to the better application of taxinol in clinical works. DATA SOURCES： We indexed the pertinent literatures in Medline database from January 1979 to February 2006 on compute by the key words of ＂chemotherapy, tumor, taxinol＂, and the language was limited to English. STUDY SELECTION： All the related articles about the mechanism and clinical application of taxinol were selected. Inclusion criteria： ①random control study, ②basic or clinical research including parallel control group. Exclusion criteria： reproducible papers or reviews. DATA EXTRACTION： After the first trail, 58 papers referred to taxinol and antieaneer mechanism Were collected. Twenty papers were random control studies, basic or clinical research including parallel control group, which accorded to the inclusion criteria; Thirty-eight papers, which were reproducibility papers or reviews, were expelled. DATA SYNTHESIS： ①Taxinol, as a broad-spectrum antieaneer drug, has satisfactory therapeutic effects for some advanced cancer which are resistant to ordinary antieaneer drugs, and has significant curative effects for many clinical malignancies. Recent study results show that taxinol has a significant eytotoxie effect to Carpse sarcoma, high effects to P388 and P1534 leukemia, and inhibition effect to the growth of W256 sarcoma, S180 and lung cancer. ②Taxinol may suppress tumor through regulating mierotubule stabilization, inducing apoptosis and adjusting immunologic mechanism. ③It is generally thought that the main target of taxinol is mierotubule protein/mierotubule system. Taxinol can promote the polymerization of mierotubule and inhibit their degradation, through which taxinol can block cell division in G2/M stage and induce apoptosis of tumor cells. However, numerous researches have indicated that the effect of taxinol to mierotubule and the blockage of cell division in G2/M stage are not the only mechanisms for the apoptosis induced by taxinol.④The novelty of taxinol＇s pharmacological action is that it can induce apoptosis through inhibiting the formation of mierotubule and regulating the dynamic balance of mierotubule protein dimer. CONCLUSION： ①Yaxinol is thought as a broad-spectrum anticancer drug, which can further promote the therapeutic effect if combined with other ordinary antieaneer drugs. Therefore taxinol is the other important antieaneer drug after eyelophosphamide and adriamyein. ②There are many signal conduction paths and mechanisms that may participate in the apoptosis reduced by taxinol.