Development of efficient production of antitumor agents originated from plant and their application to antitumor therapy using hybrid liposomes

检查了有效生产抗癌剂如紫杉醇（Taxol）和改善愈伤组织培养物中愈伤组织生长的培养条件（参见下文1-3）。为了增强紫杉醇对肿瘤细胞生长的抑制作用，制备了包括生物材料和紫杉醇的混合脂质体，并检测了它们的生长抑制作用（参见下面的4）。研究结果如下：1.从多种有机溶剂中筛选出适合于紫杉醇增溶的有机溶剂，利用疏水作用从水溶液中回收紫杉醇。脂肪烃的log P值大于5，脂肪醇和甘油三酯是很好的候选人，为增强紫杉醇的生产和改善的愈伤组织生长。在选定的有机溶剂中增溶的诱导子对紫杉醇的产生和愈伤组织的生长是有效的.泡沫具有明显的疏水性，用于从介质中回收紫杉醇，而不是有机溶剂。在愈伤组织培养中，紫杉醇在泡沫中的选择性积累，表明泡沫是紫杉醇选择性回收的良好候选材料.大规模愈伤组织培养一般采用搅拌或鼓泡塔生物反应器。研究了振荡速度对愈伤组织生长和紫杉醇产量的影响。研究了维持愈伤组织生长和紫杉醇产量的最佳振荡速度.采用生物材料提高紫杉醇在水中的溶解度。生物材料和紫杉醇的混合脂质体同时形成适当大小的脂质体，并稳定数周。此外，杂化脂质体对肿瘤细胞的生长有抑制作用。这些数据表明，杂交脂质体可能是一种新的化疗药物在治疗癌症。

Culture conditions for the effective production of antitumor agents such as Paclitaxel (Taxol) and improvement of callus growth in the callus culture were examined (refer to 1-3 below). To enhance the inhibitory effect of Taxol on the growth of tumor cells, hybrid liposomes including biological materials and Taxol were prepared and their growth inhibitory effects were also examined (refer to 4 below). The results obtained are as follows.1. Appropriate organic solvents, which solubilized Taxol easily, were selected from a variety of organic solvents to recover Taxol from the aqueous medium due to hydrophobic interaction. Aliphatic hydrocarbons having log P values of more than 5, fatty alcohols and triglycerides were good candidates for the enhancement of Taxol production and improvement of the callus growth. An elicitor solubilized in selected organic solvents was effective for the Taxol production and the callus growth.2. Foam, which has an apparently hydrophobic property, was used for the recovery of Taxol from the medium instead of the organic solvents. Selective accumulation of Taxol in the foam was observed in the callus culture, which indicated that foam had an excellent candidate for selective recovery of Taxol.3. Generally, stirred or bubble column bioreactor was utilized for the large scale callus culture. The effect of shaking speeds on the callus growth and Taxol production was examined. Optimum shaking speed for maintaining callus growth and Taxol production was examined.4. Biological materials were used to increase the solubility of Taxol in water. Hybrid liposomes including biological materials and Taxol simultaneously formed appropriate size of liposomes and were stable for several weeks. Besides, the hybrid liposomes showed an inhibitory effect on the growth of the tumor cells. The data suggest that the hybrid liposomes could be a novel chemotherapeutic agent in the treatment of cancers.