Bottone M G, Soldani C, Veneroni P, Avella D, Pisu M, Bernocchi G
Dipartimento di Biologia Animale, Università di Pavia, and Istituto di Genetica Moleculare, Sezione di Istochimica e Citochimica del CNR, Pavia, Italy.
Cell Prolif. 2008 Jun;41(3):506-20. doi: 10.1111/j.1365-2184.2008.00530.x. Epub 2008 Apr 7.
Cisplatin (cisPt) is used as a chemotherapeutic agent for the treatment of a variety of human tumours; more recently, it has been demonstrated that tumour cell exposure to cisPt ultimately results in apoptosis, but the mechanism by which nuclear cisPt/DNA generates the cytoplasmic cascade of events involved has not been clarified. We have investigated the effects of cisPt on proliferation in the neuronal cell line B50, with particular attention being given to understand whether mitochondria are a target of cisPt and their involvement in the apoptotic process.
Rat neuronal B50 cells were used to investigate the mechanisms of cisPt-induced cytotoxicity; this line has been used as a model system for neurotoxicity in vivo.
Changes in proliferation, induction of apoptosis, activation of caspase-3 and DNA fragmentation were observed in the cells, as well as morphological and biochemical alterations of mithocondria. Activation of caspase-9 confirmed that mitochondria are a target of cisPt.
CisPt exerts cytotoxic effects in the neuronal B50 cell line via a caspase-dependent pathway with mitochondria being central relay stations.
顺铂（cisPt）用作治疗多种人类肿瘤的化疗药物；最近，已证明肿瘤细胞暴露于顺铂最终会导致细胞凋亡，但细胞核内顺铂/DNA引发相关细胞质事件级联反应的机制尚未阐明。我们研究了顺铂对神经元细胞系B50增殖的影响，特别关注线粒体是否为顺铂的作用靶点以及它们在凋亡过程中的参与情况。
使用大鼠神经元B50细胞研究顺铂诱导细胞毒性的机制；该细胞系已被用作体内神经毒性的模型系统。
在细胞中观察到增殖变化、凋亡诱导、半胱天冬酶-3激活和DNA片段化，以及线粒体的形态和生化改变。半胱天冬酶-9的激活证实线粒体是顺铂的作用靶点。
顺铂通过依赖半胱天冬酶的途径在神经元B50细胞系中发挥细胞毒性作用，线粒体是核心中继站。
