Zinc pyrithione (ZPT) is widely used as an antimicrobial. Zinc is a necessary trace element of the human whose homeostasis associated with several cancers. However, the anticancer effect of increased Zinc in ovarian cancer is still unclear. This study focussed on the anti-tumour effects of ZPT combined with Zinc in SKOV3 and SKOV3/DDP cells. The cell viability, apoptosis, migration, and invasion assays were detected by CCK-8, flow cytometry, wound healing and transwell assay, respectively. The distribution of Zinc in cells was monitored by staining of Zinc fluorescent dye and lysosome tracker. The changes in lysosomal membrane stability were reflected by acridine orange fluorescence and cathepsin D reposition. Expression of the proteins about invasion and apoptosis was evaluated by western blot. The results indicated that ZPT combined with Zinc could notably reduce cell viability, inhibit migration and invasion in SKOV3 and SKOV3/DDP cells. Besides, ZPT performed as a Zinc carrier targeted lysosomes, caused the increase of its membrane permeability and the release of cathepsin D accompanied by mitochondrial apoptosis in SKOV3/DDP cells. In conclusion, our work suggests that ZPT combined with Zinc could inhibit proliferation, migration, invasion, and promote apoptosis by trigger the lysosome-mitochondrial apoptosis pathway in ovarian carcinoma.

中文翻译：

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锌离子载体巯氧吡啶酮通过抑制增殖和迁移并促进溶酶体-线粒体凋亡而在人卵巢癌细胞中具有抗肿瘤活性。

巯氧吡啶锌（ZPT）被广泛用作抗菌剂。锌是人类体内与几种癌症相关的体内稳态的必需微量元素。但是，锌在卵巢癌中的抗癌作用仍不清楚。这项研究集中于ZPT联合锌在SKOV3和SKOV3 / DDP细胞中的抗肿瘤作用。通过CCK-8，流式细胞术，伤口愈合和transwell分析分别检测细胞活力，凋亡，迁移和侵袭分析。通过锌荧光染料和溶酶体示踪剂的染色来监测锌在细胞中的分布。a啶橙荧光和组织蛋白酶D重新定位反映了溶酶体膜稳定性的变化。通过蛋白质印迹评估关于侵袭和凋亡的蛋白质的表达。结果表明，ZPT结合锌可显着降低细胞活力，抑制SKOV3和SKOV3 / DDP细胞的迁移和侵袭。此外，ZPT作为锌载体靶向的溶酶体，引起其膜通透性的增加和组织蛋白酶D的释放，伴随着线粒体在SKOV3 / DDP细胞中的凋亡。总之，我们的工作表明ZPT联合锌可以通过触发卵巢癌的溶酶体-线粒体凋亡途径来抑制增殖，迁移，侵袭并促进凋亡。