草钯对 PC3 人类前列腺癌细胞抗癌作用的体外研究。

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC
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引用次数: 0

摘要

前列腺癌是一种常见的男性癌症,发病率和死亡率都很高。我们的目的是研究草钯 (ox-Pd) 对转移性人类前列腺癌 PC3 细胞的影响,并将其与奥沙利铂 (ox-Pt) (已获批准的抗癌药物)的影响进行比较。我们通过一种新的化学方法合成了羰基钯,并利用傅立叶变换红外光谱、1H NMR、13C NMR 和 MS 分析对其进行了表征。研究了 ox-Pd 对 PC3 细胞活力、凋亡、细胞周期、迁移和基因表达的影响。通过 pHOT1 质粒松弛和 kDNA decatenation 试验研究了对拓扑异构酶 IIα 活性的抑制作用。化学测试表明,ox-Pd 具有正确的组成和结构。通过质谱分析,首次获得了氧化钯的准确碎片途径及其与氧化铂的区别。Ox-Pd 能明显降低 PC3 细胞的存活率,而对 MHFB-1 正常皮肤成纤维细胞的毒性作用较小或没有。伤口划痕试验证实 ox-Pd 具有很强的抗迁移活性。根据流式细胞术分析,该药物增加了 PC3 细胞晚期凋亡的数量,并减少了 DNA 复制和有丝分裂。此外,pHOT1 质粒松弛和 kDNA decatenation 试验表明,ox-Pd 能强烈抑制拓扑异构酶 IIα 的催化活性。在 ox-Pd 处理下,拓扑异构酶 IIα、Bcl-2、P21 和 survivin 的表达量减少,而 Bax 和 p53 的表达量增加。我们首次证明,与 ox-Pt 相比,ox-Pd 对 PC3 细胞具有更强的选择性抗癌作用。 综上所述,这些数据有力地证明了 ox-Pd 在癌症中的治疗窗口。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

In vitro study on the anticancer effects of oxalipalladium against PC3 human prostate carcinoma cells

In vitro study on the anticancer effects of oxalipalladium against PC3 human prostate carcinoma cells

In vitro study on the anticancer effects of oxalipalladium against PC3 human prostate carcinoma cells

Prostate cancer is a common type of cancer in men with high incidence and mortality. Our aim was to investigate the effects of oxalipalladium (ox-Pd) on metastatic human prostate cancer PC3 cells and compare them with the effects of oxaliplatin (ox-Pt) (as an approved cancer drug). We synthesized ox-Pd through a new chemical method and used FT-IR, 1H NMR, 13C NMR, and MS analyzes to characterize it. The effects of ox-Pd on PC3 cells viability, apoptosis, cell cycle, migration, and gene expression were examined. Inhibition of topoisomerase IIα activity was investigated by pHOT1 plasmid relaxation and kDNA decatenation assays. Chemical tests showed ox-Pd with the correct composition and structure. For the first time, the exact fragmentation pathway of ox-Pd and its difference with ox-Pt was obtained by MS analysis. Ox-Pd significantly decreased PC3 cell viability with less/no toxicity effect on MHFB-1 normal skin fibroblasts. Wound scratch assay confirmed the strong anti-migratory activity of ox-Pd. According to flow cytometry analysis, this drug increased the number of PC3 cells in late apoptosis and decreased DNA replication and mitosis. Furthermore, pHOT1 plasmid relaxation and kDNA decatenation assays showed that ox-Pd strongly inhibited the catalytic activity of topoisomerase IIα. The expression of topoisomerase IIα, Bcl-2, P21, and survivin was decreased while the expression of Bax and p53 was increased under ox-Pd treatment. We provide the first evidence that ox-Pd exhibits more selective anticancer effects on PC3 cells compared to ox-Pt. Taken together, these data strongly suggest a therapeutic window for ox-Pd in cancer.

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CiteScore
7.20
自引率
4.30%
发文量
567
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