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体外评估二联吡啶苯并嗪配合物在 H-ras 癌基因转化的大鼠胚胎成纤维细胞 5RP7 细胞系中的作用。

The in vitro assessment of dipyridophenazine complexes in H-ras oncogene transformed rat embryo fibroblast 5RP7 cell line.

机构信息

Department of Biology, Faculty of Science, Anadolu University, 26470, Eskisehir, Turkey.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Bezmialem University, 34093, İstanbul, Turkey.

出版信息

Invest New Drugs. 2018 Oct;36(5):755-762. doi: 10.1007/s10637-017-0559-4. Epub 2018 Jan 8.

Abstract

Purpose The aim of this study is to detect apoptotic and cytotoxic/antiproliferative effects of a ligand substance and its metal derivatives. The substances were investigated by using an h-ras oncogene transformed rat embryo fibroblast cell line (5RP7). Methods The cytotoxic influences of dipyrido[3,2-a:2',3'c]phenazine ligand, dipyrido[3,2-a:2',3'c] phenazine-platinum(II) complex ([Pt(dppz)Cl]) and dipyrido[3,2-a:2',3'c] phenazine-gold(III) complex ([Au(dppz)Cl]Cl) were determined with MTT (3[4,5-dimetiltiyazol2-yl]-2,5-difeniltetrazolyum bromid) assay on 5RP7 cells. Results Dipyrido[3,2-a:2',3'c] phenazine, dipyrido[3,2-a:2',3'c] phenazine-platinum(II) complex ([Pt(dppz)Cl]) and dipyrido[3,2-a:2',3'c] phenazine-gold(III) complexes ([Au(dppz)Cl]Cl) caused significant increase in cytotoxicity in a dose and time dependent manner. The effects of dipyridophenazine ligand (dppz) and its metal derivatives on apoptosis were monitorized using cytotoxic dose (10 μM) DAPI fluorescent staining. It was shown that dppz and its compounds induced apoptosis. Conclusions These findings show that dpzz and its complexes can be studied as novel alternative chemotherapeutics in cancer treatment.

摘要

目的 本研究旨在检测配体物质及其金属衍生物的凋亡和细胞毒性/抗增殖作用。使用 h-ras 癌基因转化的大鼠胚胎成纤维细胞系(5RP7)研究了这些物质。

方法 采用 MTT(3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四氮唑溴盐)测定法,测定二吡啶并[3,2-a:2',3'c]吩嗪配体、二吡啶并[3,2-a:2',3'c]吩嗪-铂(II)配合物([Pt(dppz)Cl])和二吡啶并[3,2-a:2',3'c]吩嗪-金(III)配合物([Au(dppz)Cl]Cl)对 5RP7 细胞的细胞毒性影响。

结果 二吡啶并[3,2-a:2',3'c]吩嗪、二吡啶并[3,2-a:2',3'c]吩嗪-铂(II)配合物([Pt(dppz)Cl])和二吡啶并[3,2-a:2',3'c]吩嗪-金(III)配合物([Au(dppz)Cl]Cl)均能剂量和时间依赖性地显著增加细胞毒性。采用细胞毒性剂量(10 μM)DAPI 荧光染色监测二吡啶并吩嗪配体(dppz)及其金属衍生物对细胞凋亡的影响。结果表明,dppz 及其化合物能诱导细胞凋亡。

结论 这些发现表明,dpzz 及其配合物可作为癌症治疗的新型化学治疗替代物进行研究。

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