Berchem G J, Bosseler M, Mine N, Avalosse B
Laboratoire d'Oncologie Moléculaire, Institut Jules Bordet, Brussels, Belgium.
Anticancer Res. 1999 Jan-Feb;19(1A):535-40.
Docetaxel (Taxotere), a member of the taxoid family of chemotherapy drugs is currently being tested in clinical trials simultaneously with other apoptosis inducing drugs like doxorubicin. We show, in vitro, in MCF-7 breast cancer cells that when it is used at doses as low as 5nM, 24 hours before either doxorubicin or etoposide, docetaxel is capable of inducing a significant increase in cell death compared to the reverse sequence or simultaneous treatment. We further show that this increase in cell death is due to an increase in apoptosis, and that this sensitization coincides with a docetaxel induced G2-M arrest and phosphorylation of the bcl-2 oncoprotein. We speculate that this phosphorylation of the apoptosis blocker bcl-2 might be responsible for the sensitization, and we suggest a clinical study comparing a 24 hour docetaxel pretreatment to the current simultaneous schedules.
多西他赛（泰索帝）是化疗药物紫杉烷家族的一员，目前正在与其他诱导凋亡的药物（如阿霉素）同时进行临床试验。我们在体外对MCF-7乳腺癌细胞进行研究，结果表明，与相反顺序给药或同时给药相比，当在阿霉素或依托泊苷给药前24小时以低至5nM的剂量使用多西他赛时，它能够显著增加细胞死亡。我们进一步表明，细胞死亡的增加是由于凋亡增加所致，并且这种致敏作用与多西他赛诱导的G2-M期阻滞以及bcl-2癌蛋白的磷酸化同时发生。我们推测凋亡阻断剂bcl-2的这种磷酸化可能是致敏作用的原因，并且我们建议开展一项临床研究，将多西他赛24小时预处理与当前的同时给药方案进行比较。
