Ciprofloxacin induces apoptosis and inhibits proliferation of human colorectal carcinoma cells.
Ciprofloxacin induces apoptosis and inhibits proliferation of human colorectal carcinoma cells.
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DOI：
10.1038/sj.bjc.6600079
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发表时间：
2002-02-01
影响因子：
8.8
通讯作者：
Schuppan, D
中科院分区：
文献类型：
--
作者：
Herold, C;Ocker, M;Ganslmayer, M;Gerauer, H;Hahn, E G;Schuppan, D
化疗在晚期结直肠肿瘤中的疗效有限。喹诺酮类抗生素环丙沙星最近被证明能抑制人膀胱癌细胞的生长并诱导细胞凋亡。我们研究了环丙沙星对体外培养的结肠癌细胞株的作用。将CC-531、SW-403和HT-29结肠癌和HepG 2肝癌细胞（对照细胞）暴露于环丙沙星。通过溴脱氧尿苷掺入DNA评估增殖，并在碘化丙啶或JC-1染色后通过流式细胞术测量凋亡。抗凋亡Bcl-2和促凋亡Bax的表达通过半定量Western印迹分析和半胱天冬酶3、8和9的活性通过底物切割测定进行分析。环丙沙星抑制所有结肠癌细胞的DNA合成的时间和剂量依赖性，而肝癌细胞不受影响。细胞凋亡在200 - 500 μg ml−1之间达到最大值。这是伴随着上调Bax和半胱天冬酶3，8和9的活性，并通过线粒体膜电位的降低而抑制。环丙沙星抑制结肠癌细胞增殖并诱导凋亡，可能部分通过阻断线粒体DNA合成。因此，应评价环丙沙星作为结直肠癌治疗药物的可行性。英国癌症杂志（2002）86，443-448。DOI：10.1038/sj/bjc/6600079 www.bjcancer.com © 2002癌症研究运动
Efficacy of chemotherapy in advanced stages of colorectal tumours is limited. The quinolone antibiotic ciprofloxacin was recently shown to inhibit growth and to induce apoptosis in human bladder carcinomas cells. We investigated the effect of ciprofloxacin on colon carcinoma lines in vitro. CC-531, SW-403 and HT-29 colon carcinoma and HepG2 hepatoma cells (control cells) were exposed to ciprofloxacin. Proliferation was assessed by bromodeoxyuridine-incorporation into DNA and apoptosis was measured by flow cytometry after propidium iodide or JC-1 staining. Expression of anti-apoptotic Bcl-2 and pro-apoptotic Bax was analyzed by semiquantitative Western blot analysis and activity of caspases 3, 8 and 9 by substrate-cleavage assays. Ciprofloxacin suppressed DNA synthesis of all colon carcinoma cells time- and dose-dependently, whereas the hepatoma cells remained unaffected. Apoptosis reached its maximum between 200 and 500 μg ml−1. This was accompanied by an upregulation of Bax and of the activity of caspases 3, 8 and 9, and paralleled by a decrease of the mitochondrial membrane potential. Ciprofloxacin decreases proliferation and induces apoptosis of colon carcinoma cells, possibly in part by blocking mitochondrial DNA synthesis. Therefore, qualification of ciprofloxacin as adjunctive agent for colorectal cancer should be evaluated. British Journal of Cancer (2002) 86, 443–448. DOI: 10.1038/sj/bjc/6600079 www.bjcancer.com © 2002 The Cancer Research Campaign