Buxant Frederic, Kindt Nadège, Noël Jean-Christophe, Laurent Guy, Saussez Sven
Department of Gynaecology, Iris South Hospital, Brussels.
Department of Anatomy, Laboratory of Anatomy and Cell Biology, Faculty of Medicine and Pharmacy, University of Mons, Mons.
Breast Cancer (Dove Med Press). 2017 Mar 16;9:171-175. doi: 10.2147/BCTT.S120005. eCollection 2017.
Glucocorticoids (GCs) are often administered prior to any chemotherapeutics to prevent the secondary effects of anticancer agents. Glucocorticoid receptors (GRs) are expressed in several types of cancer cells, particularly in several histological types of breast cancer. Activation of GRs is not associated with any specific cellular response. Both proapoptotic and antiapoptotic responses have been observed, depending on the study or the type of breast cancer cells. Therefore, it is of relevance to investigate the possible modulation of apoptotic effect of chemotherapeutic agents when cancerous cells have previously been exposed to GCs.
In vitro cell growth was assayed by counting MCF-7 cells upon exposure to epirubicin (25 nM), 5-fluorouracil (5-FU) (15 µM), and paclitaxel (15 nM), either with or without prior exposure to the GC dexamethasone (Dex) (100 nM).
Following preexposure to Dex, the antiapoptotic activity of paclitaxel was significantly reduced by 8.5% (<0.05), but the activities of epirubicin and 5-FU remained unaltered.
In light of the finding that the response of MCF-7 cells pretreated with Dex was significantly reduced, we recommend that the function of GCs should be defined more precisely if they are to be used in conjunction with chemotherapy.
糖皮质激素（GCs）常在任何化疗药物之前使用，以预防抗癌药物的副作用。糖皮质激素受体（GRs）在多种类型的癌细胞中表达，尤其是在几种组织学类型的乳腺癌中。GRs的激活与任何特定的细胞反应均无关联。根据研究或乳腺癌细胞类型的不同，已观察到促凋亡和抗凋亡反应。因此，研究当癌细胞先前已暴露于GCs时化疗药物凋亡效应的可能调节具有重要意义。
通过计数暴露于表柔比星（25 nM）、5-氟尿嘧啶（5-FU）（15 μM）和紫杉醇（15 nM）后的MCF-7细胞来检测体外细胞生长情况，细胞暴露于这些药物时有无预先暴露于糖皮质激素地塞米松（Dex）（100 nM）。
预先暴露于Dex后，紫杉醇的抗凋亡活性显著降低了8.5%（<0.05），但表柔比星和5-FU的活性未改变。
鉴于预先用Dex处理的MCF-7细胞反应显著降低这一发现，我们建议如果要将GCs与化疗联合使用，应更精确地定义其功能。
