El-Rayes Basil F, Grignon Robert, Aslam Naveed, Aranha Olivia, Sarkar Fazlul H
Department of Hematology/Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Int J Oncol. 2002 Jul;21(1):207-11.
Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer related deaths in men in the United States. Ciprofloxacin is a relatively non-toxic antibiotic that can be easily administered orally with large volume of distribution and good tissue penetration. Studies from others and our laboratory have recently reported its anti-tumor activity in a variety of human tumor cells. In our current experiment, we studied the effect of ciprofloxacin on a hormone resistant prostate cancer (HRPC) cell line, PC-3. Our study shows significant in vitro cell growth inhibition of PC-3 cell line (p=0.0001) and also shows that there is a synergistic increase in the antiproliferative effect of etoposide when these cells are pretreated with ciprofloxacin for 24 h, prior to etoposide exposure (p=0.0001). Western blot analysis of the protein extracts from these cells showed down-regulation of Bcl-2, altering the ratio of Bax:Bcl-2 favoring apoptosis. In our study no significant effect was seen on p21WAF1 expression by the combination of ciprofloxacin and etoposide but there was down-regulation of p21WAF1 gene by ciprofloxacin alone. Ciprofloxacin also inhibited NF-kappaB binding to DNA. Further studies in this area are warranted as the roles of p21WAF1, Bax/Bcl-2 and NF-kappaB may be important molecular events in mediating the antiproliferative and apoptosis inducing effect of etoposide in combination with ciprofloxacin in HRPC cells.
前列腺癌是美国男性中最常被诊断出的癌症，也是癌症相关死亡的第二大主要原因。环丙沙星是一种相对无毒的抗生素，易于口服，分布容积大，组织穿透力强。其他研究机构和我们实验室的研究最近报道了其在多种人类肿瘤细胞中的抗肿瘤活性。在我们当前的实验中，我们研究了环丙沙星对激素抵抗性前列腺癌（HRPC）细胞系PC-3的影响。我们的研究表明，PC-3细胞系在体外有显著的细胞生长抑制作用（p = 0.0001），并且还表明，在暴露于依托泊苷之前，先用环丙沙星预处理这些细胞24小时，依托泊苷的抗增殖作用会协同增强（p = 0.0001）。对这些细胞的蛋白质提取物进行的蛋白质印迹分析显示，Bcl-2表达下调，改变了Bax:Bcl-2的比例，有利于细胞凋亡。在我们的研究中，环丙沙星和依托泊苷联合使用对p21WAF1表达没有显著影响，但单独使用环丙沙星会使p21WAF1基因下调。环丙沙星还抑制NF-κB与DNA的结合。由于p21WAF1、Bax/Bcl-2和NF-κB的作用可能是介导依托泊苷与环丙沙星联合使用对HRPC细胞的抗增殖和诱导凋亡作用的重要分子事件，因此有必要在这一领域进行进一步研究。
