Grimaldi Maddalena, Santin Giada, Insolia Violetta, Dal Bo Veronica, Piccolini Valeria Maria, Veneroni Paola, Barni Sergio, Verri Manuela, De Pascali Sandra Angelica, Fanizzi Francesco Paolo, Bernocchi Graziella, Bottone Maria Grazia
Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, Via Ferrata 9, 27100, Pavia, Italy.
Department of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, Lecce, Italy.
Histochem Cell Biol. 2016 May;145(5):587-601. doi: 10.1007/s00418-015-1396-1. Epub 2016 Jan 9.
Cisplatin is one of the most active chemotherapeutic agents used in the treatment of childhood and adult malignancies. Cisplatin induces cell death through different pathways. Despite its effectiveness, the continued clinical use of cisplatin is limited by onset of severe side effects (nephrotoxicity, ototoxicity and neurotoxicity) and drug resistance. Therefore, one of the main experimental oncology purpose is related to the search for new platinum-based drugs to create different types of adducts or more specific and effective subcellular targets. Thus, [Pt(O,O'-acac)(γ-acac)(DMS)], which reacts preferentially with protein thiols or thioether, was synthesized. In our research, different approaches were used to compare cisplatin and [Pt(O,O'-acac)(γ-acac)(DMS)] effects in B50 rat neuroblastoma cells. Our results, using immunocytochemical, cytometric and morphological techniques, showed that these compounds exert a cytostatic action and activate apoptosis with different pathways. Long-term effects demonstrated that [Pt(O,O'-acac)(γ-acac)(DMS)] exerts cytotoxic effects in neuronal B50 cell line not inducing drug resistance. Analysis was performed both to compare the ability of these platinum compounds to induce cell death and to investigate the intracellular mechanisms at the basis of their cytotoxicity.
顺铂是用于治疗儿童和成人恶性肿瘤的最有效的化疗药物之一。顺铂通过不同途径诱导细胞死亡。尽管其疗效显著,但顺铂的持续临床应用受到严重副作用(肾毒性、耳毒性和神经毒性)的出现以及耐药性的限制。因此,肿瘤学实验的主要目的之一是寻找新的铂类药物,以形成不同类型的加合物或更特异、有效的亚细胞靶点。因此,合成了[Pt(O,O'-乙酰丙酮)(γ-乙酰丙酮)(二甲基硫醚)],它优先与蛋白质硫醇或硫醚反应。在我们的研究中,采用了不同方法比较顺铂和[Pt(O,O'-乙酰丙酮)(γ-乙酰丙酮)(二甲基硫醚)]对B50大鼠神经母细胞瘤细胞的作用。我们利用免疫细胞化学、细胞计量学和形态学技术得到的结果表明,这些化合物发挥细胞生长抑制作用,并通过不同途径激活细胞凋亡。长期效应表明,[Pt(O,O'-乙酰丙酮)(γ-乙酰丙酮)(二甲基硫醚)]对神经元B50细胞系具有细胞毒性作用,且不会诱导耐药性。进行分析既是为了比较这些铂化合物诱导细胞死亡的能力,也是为了研究其细胞毒性背后的细胞内机制。