红豆杉高产悬浮细胞系建立及其紫杉醇诱导的研究进展

Research progress in high yielding suspension cell lines and the induction of Taxol in Taxus

关键词:  红豆杉, 抗癌药物, 细胞培养, 悬浮细胞系建立, 紫杉醇诱导

Key words:  Taxus, anticancer drugs, cell culture, suspension cell lines, Taxol induced

摘要:

紫杉醇是一种四环二萜酰胺类化合物,是从红豆杉科红豆杉属植物中提取分离出来的次生代谢物,是世界公认广谱、活性强的天然抗癌新药。但直接从植物中提取紫杉醇的传统生产方式,不仅产量低,且会对野生红豆杉资源造成严重破坏,同时紫杉醇的化学全合成也由于其结构复杂而不具备商业价值。与之相反,细胞培养技术具有受外界影响少、生产成本低、次生代谢产物多、细胞生长周期短的优势,是目前最具前景的紫杉醇生产方式。近年来随着科研水平的不断提升,紫杉醇无论在生理代谢调控、关键基因挖掘,还是新药物制剂与剂型及其类似物的开发和运用等方面,都取得了进展,但要建立紫杉醇商业化高产体系,还必须和前人的研究经验相结合。该文对红豆杉高产悬浮细胞系建立及其紫杉醇诱导的研究进展进行了综述,主要包括前人对红豆杉属植物组织与细胞培养相关的外植体、培养基、激素、培养条件、褐化等问题的研究,以及从代谢调节、培养方式、基因工程等多方面提高紫杉醇含量的最新进展,最后总结了当前研究的不足,并对今后通过多种组合方式来提高紫杉醇含量的生产途径进行了展望。以期促进红豆杉组织培养技术的进步,为药用资源保护和利用提供一定的理论基础与生产指导

Abstract:

Taxol, a diterpene alkaloid secondary metabolite of Taxus species, has been considered as one of the most promising anticancer drugs used for the treatment of several types of cancer. However, due to the difficulties in obtaining enough this compound from Taxus trees, the traditional approach extracted directly from plants not only produces low yield, but also triggers serious damage to the wild resource of Taxus. At the same time, the complex structure Taxol has impeded efforts to find a method to fulfill an economically feasible strategy via total synthesis. By constrast, cell culture of Taxus is a potential alternative for the production of Taxol and analogue compounds in a large scale culture, which possesses a multitude of advantages such as high purity product of secondary metabolite, low production cost, short cell growth cycle and less influence from external factors. Huge efforts have been made to develop a more sustainable source of Taxol. The main target of ongoing Taxus-related research in recent years are on the regulation of Taxus metabolism, key genes mining, application and development in new pharmaceutical preparations. Different ways, including application of precursors and elicitors, optimizing of cultural conditions, screening of high yielding cell lines, optimization of growth and production media, have been already tested to improve the yield of Taxol in cultures of Taxus. It is necessary to take into account the latest achievements based on empirical procedures to establish a high yielding system. In this review, we have summarized the latest endeavors to establish a high yield suspension cell line and increase its yield of Taxol, with a special focus on the key issues related to tissue culture of Taxus such as explants, culture medium, hormone treatment, culture conditions, browning and other issues. Developments for new and more effective elicitation treatments and the application of metabolic engineering to design new transgenic cell lines of Taxus with an improved capacity for taxane production have also been described. In the end, the article discusses the faultiness of current researches and prospects various combinational methods for raising Taxol content. This paper is helpful for promoting technology progress of tissue culture in Tuaxs and it will provide the guidance for the protection and application of medicinal resources.