Cyclooxygenase-2 inhibitors suppress the growth of human hepatocellular carcinoma implants in nude mice
Cyclooxygenase-2 inhibitors suppress the growth of human hepatocellular carcinoma implants in nude mice
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DOI：
10.1093/carcin/bgh110
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发表时间：
2004-07-01
期刊：
影响因子：
4.7
通讯作者：
Schirmacher, P
中科院分区：
文献类型：
--
作者：
Kern, MA;Schöneweiss, MM;Schirmacher, P
环氧合酶 (COX)-2 在肝细胞癌 (HCC) 和 HCC 细胞系中表达。 COX-2 抑制可通过诱导细胞凋亡和减少增殖来强烈抑制体外 HCC 细胞的生长。在这里，我们评估了COX-2抑制人肝癌细胞系来源的裸鼠异种移植肿瘤的体内效果和机制。首先，在注射肿瘤细胞前5天开始，用COX-2特异性抑制剂（美洛昔康）或非特异性抑制剂（舒林酸）治疗裸鼠。 35天后，处死小鼠并对肿瘤进行形态学分析并测定增殖（Ki67）、细胞凋亡（M30）和COX-2表达。其次，在肿瘤直径达到至少0.2厘米后，用美洛昔康或舒林酸治疗小鼠。 COX-2 表达在植入肿瘤中维持在与亲代细胞相当的水平。选择性 COX-2 抑制导致肿瘤生长和重量显着减少。 COX-2抑制对肿瘤细胞具有显着的抗增殖和促凋亡作用。这些结果表明，在实验条件下，选择性 COX-2 抑制可抑制体内实体 HCC 的生长，因此可能对人类 HCC 具有预防和治疗潜力。
Cyclooxygenase (COX)-2 is expressed in hepatocellular carcinomas (HCCs) and HCC cell lines. COX-2 inhibition strongly suppresses growth of HCC cells in vitro by inducing apoptosis and reducing proliferation. Here, we evaluate the in vivo effects and mechanism of COX-2 inhibition of human HCC cell line derived xenotransplanted tumors in nude mice. Firstly, nude mice were treated with a COX-2 specific inhibitor (meloxicam) or a non-specific inhibitor (sulindac) starting 5 days prior to tumor cell injection. After 35 days mice were killed and tumors were analyzed morphologically and assayed for proliferation (Ki67), apoptosis (M30) and COX-2 expression. Secondly, mice were treated with meloxicam or sulindac after tumors had reached a diameter of at least 0.2 cm. COX-2 expression was maintained in implant tumors at levels comparable with parental cells. Selective COX-2 inhibition led to a significant reduction of tumor growth and weight. COX-2 inhibition had a significant anti-proliferative and pro-apoptotic effect on tumor cells. These results demonstrate that under experimental conditions selective COX-2 inhibition suppresses solid HCC growth in vivo and, therefore may have preventive and therapeutic potential for human HCCs.