Bielecka A M, Obuchowicz E
Department of Pharmacology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
Eur J Cancer Care (Engl). 2017 Sep;26(5). doi: 10.1111/ecc.12551. Epub 2016 Aug 2.
Cancer patients often require antidepressant treatment due to comorbid depressive disorder. However, recent studies have demonstrated that antidepressant drugs affect the efficacy of chemotherapy and promote progression of cancer. Apart from the main mood-improving effect, antidepressant drugs also produce analgesic, anxiolytic, hypnotic and pro-cognitive actions. Patients suffering from brain cancer constitute the greatest percentage of depressive cancer patients. However, vital safety and efficacy issues related to combined therapy with temozolomide, the first-line cytostatic in patients diagnosed with glioblastoma multiforme, and antidepressant drugs have yet to be addressed. The aim of the present studies was to evaluate the effect of three antidepressant drugs (imipramine, fluoxetine and tranylcypromine) on the cytotoxic efficacy of temozolomide on T98G cells, a human glioblastoma cell line. In our experiments, we used a complex experimental in vitro system to mimic the instability of a tumour's oxygen supply, thereby reproducing conditions that occur inside the tumour. The effect of the interaction between temozolomide and antidepressant drugs on viability, apoptosis and intensity of divisions of glioblastoma cells was evaluated under different oxygen conditions. The results of our studies demonstrated that imipramine and tranylcypromine reduced the cytotoxic efficacy of temozolomide under some oxygen conditions while fluoxetine did not demonstrate such effects.
癌症患者常因合并抑郁症而需要抗抑郁治疗。然而，最近的研究表明，抗抑郁药物会影响化疗效果并促进癌症进展。除了主要的改善情绪作用外，抗抑郁药物还具有镇痛、抗焦虑、催眠和促认知作用。脑癌患者在抑郁癌症患者中占比最大。然而，对于多形性胶质母细胞瘤患者一线使用的细胞抑制剂替莫唑胺与抗抑郁药物联合治疗相关的重要安全性和有效性问题尚未得到解决。本研究的目的是评估三种抗抑郁药物（丙咪嗪、氟西汀和反苯环丙胺）对替莫唑胺对人胶质母细胞瘤细胞系T98G细胞的细胞毒性作用的影响。在我们的实验中，我们使用了一个复杂的体外实验系统来模拟肿瘤氧气供应的不稳定性，从而再现肿瘤内部发生的情况。在不同氧气条件下，评估替莫唑胺与抗抑郁药物相互作用对胶质母细胞瘤细胞活力、凋亡和分裂强度的影响。我们的研究结果表明，在某些氧气条件下，丙咪嗪和反苯环丙胺会降低替莫唑胺的细胞毒性作用，而氟西汀则未表现出此类作用。
