Fabbri Raffaella, Macciocca Maria, Vicenti Rossella, Paradisi Roberto, Klinger Francesca Gioia, Pasquinelli Gianandrea, Spisni Enzo, Seracchioli Renato, Papi Alessio
Gynecology & Pathophysiology of Human Reproductive Unit, Department of Medical & Surgical Sciences, University of Bologna, S Orsola-Malpighi Hospital, Bologna, Italy.
Department of Biomedicine & Prevention, University of Rome Tor Vergata, Rome, Italy.
Future Oncol. 2016 Jul;12(14):1699-711. doi: 10.2217/fon-2016-0032. Epub 2016 May 13.
To investigate mechanisms by which doxorubicin (DOX) and cisplatin (CIS) cause human ovarian stroma injury.
PATIENTS & METHODS: Stromal cells from human cryopreserved ovarian tissue were cultured in the presence of 1 µM DOX and 10 µM CIS. Ovarian damage induced by treatments was evaluated by 'Live/Dead' and sulforhodamine-B assays, the expression of different apoptosis markers.
Stromal cell growth was inhibited by DOX and CIS, and this effect was accompanied by apoptosis through mitochondrial pathway activation: Bax, cleaved-caspase 9, cleaved-PARP1 induction and Akt1, Bcl2, phospho-44/42-MAPK/ERK1/2 reduction were observed.
DOX and CIS induced apoptosis in human ovarian stromal cells. Knowledge of mechanisms by which the drugs act is important to identify possible ways to counteract side effects of chemotherapy on ovaries.
研究阿霉素（DOX）和顺铂（CIS）导致人卵巢基质损伤的机制。
将人冷冻保存卵巢组织中的基质细胞在1 μM DOX和10 μM CIS存在的情况下进行培养。通过“活/死”和磺酰罗丹明B检测、不同凋亡标志物的表达来评估处理诱导的卵巢损伤。
DOX和CIS抑制基质细胞生长，且这种作用伴随着通过线粒体途径激活的凋亡：观察到Bax、裂解的半胱天冬酶9、裂解的PARP1的诱导以及Akt1、Bcl2、磷酸化44/42 - MAPK/ERK1/2的减少。
DOX和CIS诱导人卵巢基质细胞凋亡。了解药物作用机制对于确定抵消化疗对卵巢副作用的可能方法很重要。
