咖啡因和己酮可可碱对人卵巢癌细胞系顺铂抗肿瘤活性的体外增强作用

In vitro enhancement of cis-platinum antitumor activity by caffeine and pentoxifylline in a human ovarian cell line.

作者信息

Schiano M A, Sevin B U, Perras J, Ramos R, Wolloch E H, Averette H E

机构信息

Department of Obstetrics and Gynecology, University of Miami School of Medicine, Florida 33101.

出版信息

Gynecol Oncol. 1991 Oct;43(1):37-45. doi: 10.1016/0090-8258(91)90006-q.

DOI:10.1016/0090-8258(91)90006-q

PMID:1959786

Abstract

Cell kinetic perturbations measuring DNA and nuclear protein with dual-parameter flow cytometry were studied in vitro after cis-platinum (DDP) treatment of a DDP-resistant human ovarian cell line (BG-1). Cell viability (trypan blue exclusion) and the cell's ability to replicate (replicating potential) are also reported. A dose-dependent G2 arrest and concomitant increase in cytotoxicity were observed. We also observed a marked increase in cytotoxicity of 2.5 micrograms/ml DDP with the addition of 1 mM of caffeine (CAF) or pentoxifylline (PTX). Additionally, the cells treated with DDP and CAF or DDP and PTX demonstrated a markedly diminished ability to replicate. Cell cycle perturbations, especially the G2-phase arrest, were markedly enhanced in the cells treated with DDP and CAF or DDP and PTX, when compared to that in cells treated with DDP alone. We conclude that the cytotoxicity of DDP is enhanced by CAF and PTX in vitro by inhibiting DNA repair during the S and G2 phases.

摘要

在用顺铂（DDP）处理耐DDP的人卵巢癌细胞系（BG-1）后，体外研究了用双参数流式细胞术测量DNA和核蛋白的细胞动力学扰动。还报告了细胞活力（台盼蓝排斥法）和细胞复制能力（复制潜力）。观察到剂量依赖性的G2期阻滞和细胞毒性随之增加。我们还观察到，添加1 mM咖啡因（CAF）或己酮可可碱（PTX）后，2.5微克/毫升DDP的细胞毒性显著增加。此外，用DDP和CAF或DDP和PTX处理的细胞显示出明显降低的复制能力。与单独用DDP处理的细胞相比，用DDP和CAF或DDP和PTX处理的细胞中，细胞周期扰动，尤其是G2期阻滞，明显增强。我们得出结论，在体外，CAF和PTX通过抑制S期和G2期的DNA修复增强了DDP的细胞毒性。