Minarik L, Hall E J
Center for Radiological Research, College of Physicians and Surgeons of Columbia University, New York, NY 10032.
Radiother Oncol. 1994 Aug;32(2):124-8. doi: 10.1016/0167-8140(94)90098-1.
Taxol is an investigational antineoplastic agent which acts by stabilizing microtubules, thereby preventing normal mitosis. It is believed to block cells in the G2/M phase of the cell cycle. The drug is a natural product isolated from the yew, Taxus brevifolia. We have used a cell line derived from human cervical carcinoma to investigate the combination of Taxol with high and low dose rate 137Cs irradiation. An additive effect for Taxol plus radiation was observed; supra-additivity or synergism is not suggested by our data. In the cell line studied, drug concentrations that accumulate cells to some degree in the G2/M phase of the cycle lead to cell lethality, so that no radiosensitizing effect is possible. We have also shown that the cytotoxic effect of Taxol is not limited to the G2/M phase of the cell cycle. In the clinic, Taxol shows promise both as a chemotherapeutic agent and as a possible adjunct to radiation. The present work demonstrates the need for further studies of Taxol plus radiation with a variety of human cell lines of normal and malignant origin.
紫杉醇是一种实验性抗肿瘤药物,其作用机制是稳定微管,从而阻止正常的有丝分裂。据信它能使细胞周期阻滞在G2/M期。该药物是从短叶红豆杉中分离出的一种天然产物。我们使用了一种源自人宫颈癌的细胞系来研究紫杉醇与高剂量率和低剂量率137Cs照射的联合作用。观察到紫杉醇加放疗有相加效应;我们的数据未表明有超相加或协同作用。在所研究的细胞系中,能使细胞在周期的G2/M期有一定程度积累的药物浓度会导致细胞死亡,因此不可能有放射增敏作用。我们还表明,紫杉醇的细胞毒性作用并不局限于细胞周期的G2/M期。在临床上,紫杉醇作为一种化疗药物以及作为放疗的可能辅助药物都显示出前景。目前的工作表明需要进一步研究紫杉醇与各种正常和恶性来源的人类细胞系联合放疗的情况。