Pulkkinen J O, Pekkola-Heino K, Grénman R
Department of Otorhinolaryngology, University of Turku, Finland.
Anticancer Res. 1996 Sep-Oct;16(5A):2923-9.
Paclitaxel (Taxol) is a new antimicrotubule plant product, which not only stabilizes the microtubules by inhibiting their disassembly but also promotes the assembly of microtubules. This causes a block in the G2-M phase of the cell cycle known to be a radiosensitive phase of the cycle. Previously we demonstrated that 10 nM paclitaxel accumulated the cells of laryngeal carcinoma cell lines in the G2-M phase as measured by flow cytometry. Time-lapse videomicroscopy demonstrated that the cells died morphologically by apoptosis after a premitotic block. Agarose gel electrophoresis showed the DNA-laddering typical of apoptosis. To investigate the effects of irradiation and paclitaxel separately and concomitantly, we used five newly established laryngeal carcinoma cell lines. The effects were recorded with time-lapse videomicroscopy over 96 hours on controls, cells irradiated with 2 Gy, cells exposed to 1 nM or 5 nM paclitaxel and cells irradiated with 2 Gy after incubating in 1 nM or 5 nM paclitaxel for 24 hours. Spontaneous apoptoses were seen in all cell lines tested. The 2 Gy irradiation dose induced a propagated apoptotic response in two of these cell lines. In all cell lines paclitaxel induced a premitotic block only in some cells at the tested concentrations and these cells died morphologically by apoptosis, whereas irradiation and paclitaxel concomitantly caused an additive inhibition in mitotic activity and caused an additive apoptotic response. An additive effect of paclitaxel and radiation was seen with doses readily achievable in clinical treatment. This additive effect seems to be due to other mechanisms of action than the premitotic block.
紫杉醇（泰素）是一种新型抗微管植物产物，它不仅通过抑制微管解聚来使其稳定，还能促进微管组装。这会导致细胞周期的G2-M期阻滞，而该期已知是细胞周期中的放射敏感阶段。此前我们通过流式细胞术检测发现，10 nM紫杉醇可使喉癌细胞系的细胞在G2-M期积聚。延时视频显微镜观察显示，细胞在有丝分裂前阻滞之后会发生凋亡，形态上表现为细胞死亡。琼脂糖凝胶电泳显示出典型的凋亡DNA梯状条带。为了分别及同时研究辐射和紫杉醇的作用，我们使用了五个新建立的喉癌细胞系。通过延时视频显微镜记录了96小时内对照组、接受2 Gy辐射的细胞、暴露于1 nM或5 nM紫杉醇的细胞以及在1 nM或5 nM紫杉醇中孵育24小时后接受2 Gy辐射的细胞的情况。在所测试的所有细胞系中均可见自发凋亡。2 Gy的辐射剂量在其中两个细胞系中诱导了一种扩展性凋亡反应。在所有细胞系中，在所测试的浓度下，紫杉醇仅在部分细胞中诱导了有丝分裂前阻滞，这些细胞在形态上因凋亡而死亡，而辐射与紫杉醇同时作用时，对有丝分裂活性产生了相加性抑制，并引发了相加性凋亡反应。在临床治疗中易于达到的剂量下，观察到了紫杉醇与辐射的相加效应。这种相加效应似乎是由有丝分裂前阻滞以外的其他作用机制所致。
