Karantanis E, Nicholson S, Morris D L
Department of Surgery, University of New South Wales, St George Hospital, Kogarah, Sydney, Australia.
Eur J Surg Oncol. 1994 Dec;20(6):653-7.
Taxotere a semisynthetic analogue of taxol, is prepared from a precursor extracted from needles of the tree, Taxus baccata. It is a mitotic spindle poison more potent than taxol, that increases the rate of microtubule assembly and inhibits depolymerization of microtubules. There has been little research on its effects on colorectal cancer. Five colorectal tumour cell lines were investigated using three modes: flow cytometry (to determine how Taxotere affects the cell cycle), MTT assay, (to examine the cytotoxicity of the drug), and measurement of tritiated thymidine uptake, (to see whether Taxotere affects the rate of DNA synthesis and cell turnover). A time-course experiment, using flow cytometry, showed effects beginning between 0 and 2 hours after exposure. 24-hour assays were conducted for flow cytometry, and showed large changes, arresting most cells in G2/M phases (e.g., cell line LIM 1215 exposed to 1 x 10(-6) M Taxotere showed 72% of cells in G2/M compared to 14.7% in controls). 24 and 48 hour assays were conducted for MTT and measurement of tritiated thymidine uptake. MTT showed significant inhibitory effects, with maximum inhibitions varying between 5 and 70% for different cell lines after 48 hours (P < 0.05), while uptake of tritiated thymidine was not altered. While Taxotere has dose-limited toxicity, our results suggest that many human colonic cancers will be sensitive to Taxotere.
泰索帝是紫杉醇的半合成类似物，由从欧洲红豆杉针叶中提取的前体物质制备而成。它是一种比紫杉醇更强效的有丝分裂纺锤体毒素，能提高微管组装速率并抑制微管解聚。关于其对结直肠癌的影响，相关研究较少。使用三种方法对五种结直肠肿瘤细胞系进行了研究：流式细胞术（以确定泰索帝如何影响细胞周期）、MTT 法（检测该药物的细胞毒性）以及测量氚标记胸腺嘧啶核苷摄取量（以观察泰索帝是否影响 DNA 合成速率和细胞更新）。一项使用流式细胞术的时间进程实验表明，在暴露后 0 至 2 小时之间开始出现影响。针对流式细胞术进行了 24 小时检测，结果显示有很大变化，大多数细胞停滞在 G2/M 期（例如，暴露于 1×10⁻⁶ M 泰索帝的 LIM 1215 细胞系中，72%的细胞处于 G2/M 期，而对照组为 14.7%）。针对 MTT 和氚标记胸腺嘧啶核苷摄取量测量进行了 24 小时和 48 小时检测。MTT 显示出显著的抑制作用，48 小时后不同细胞系的最大抑制率在 5%至 70%之间（P < 0.05），而氚标记胸腺嘧啶核苷的摄取未发生改变。虽然泰索帝存在剂量限制性毒性，但我们的结果表明，许多人类结肠癌对泰索帝将敏感。
