Host cyclooxygenase-2 modulates carcinoma growth
Host cyclooxygenase-2 modulates carcinoma growth
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DOI：
10.1172/jci9621
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发表时间：
2000-06-01
影响因子：
15.9
通讯作者：
DuBois, RN
中科院分区：
文献类型：
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作者：
Williams, CS;Tsujii, M;DuBois, RN
环氧化酶-2 （COX-2; Ptgs2）在啮齿动物结直肠癌模型中作为肿瘤启动子，但其在癌变中的确切作用尚不清楚。我们使用遗传和药理学方法评估了宿主来源的COX-1和COX-2在肿瘤生长中的作用。Lewis肺癌（LLC）细胞在C57BL/G小鼠体内快速生长为实体瘤。我们发现COX-2（-/-）小鼠的肿瘤生长明显减弱，但COX-1（-/-）或野生型小鼠则没有。用选择性COX-2抑制剂治疗患有LLC肿瘤的野生型C57BL/6小鼠也可降低肿瘤生长。与野生型小鼠相比，COX-2（-/-）小鼠肿瘤中血管密度降低。由于COX-2在人类和啮齿动物结直肠癌的间质成纤维细胞中表达，我们评估了COX-2（-/-）小鼠成纤维细胞，发现其产生促血管生成因子VEGF的能力降低了94%。此外，用选择性COX-2抑制剂治疗野生型小鼠成纤维细胞可减少92%的VEGF生成。
Cyclooxygenase-2 (COX-2; Ptgs2) acts as a tumor promoter in rodent models for colorectal cancer, but its precise role in carcinogenesis remains unclear. We evaluated the contribution of host-derived COX-1 and COX-2 in tumor growth using both genetic and pharmacological approaches. Lewis lung carcinoma (LLC) cells grow rapidly as solid tumors when implanted in C57BL/G mice. We found that tumor growth was markedly attenuated in COX-2(-/-), but not COX-1(-/-) or wild-type mice. Treatment of wild-type C57BL/6 mice bearing LLC tumors with a selective COX-2 inhibitor also reduced tumor growth. A decrease in vascular density was observed in tumors grown in COX-2(-/-) mice when compared with those in wild-type mice. Because COX-2 is expressed in stromal fibroblasts of human and rodent colorectal carcinomas, we evaluated COX-2(-/-) mouse fibroblasts and found a 94% reduction in their ability to produce the proangiogenic factor, VEGF. Additionally, treatment of wild-type mouse fibroblasts with a selective COX-2 inhibitor reduced VEGF production by 92%.