循环氧化原酶调节由结肠癌细胞诱导的血管生成
1Department of Medicine, Vanderbilt University Medical Center, VA Medical Center, Nashville, Tennessee 37232, USA.
Cell
|June 18, 1998
概括
癌细胞中的循环氧化酶-2 (COX-2) 通过产生益血管性因素促进血管生成. 内皮细胞中的循环氧化酶-1 (COX-1) 也驱动血管生成,突出了COX酶在瘤血管化中的独特作用.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 细胞生物学 细胞生物学
背景情况:
- 内皮细胞迁移和血管生成是瘤生长和转移的关键过程.
- 循环氧化原酶 (COX) 酶在炎症和细胞增殖中发挥作用,但它们在血管生成中的特定作用尚未完全阐明.
- 结肠癌细胞可以诱导血管生成,这是瘤存活和扩张至关重要的过程.
研究的目的:
- 研究循环氧化酶-1 (COX-1) 和循环氧化酶-2 (COX-2) 在内皮细胞迁移和血管生成中的不同作用.
- 确定结肠癌细胞和内皮细胞中的COX酶如何促进瘤诱导的血管生成.
主要方法:
- 使用了内皮细胞和结肠癌细胞的体外共同培养模型.
- 在癌细胞中操纵COX-2表达,并使用选择性COX-2抑制剂 (NS-398) 和阿司匹林.
- 研究了使用阿司匹林和反感性寡核酸对内皮细胞的COX-1抑制的影响.
主要成果:
- 过度表达COX-2的结肠癌细胞产生前列腺素和益血管原因子,显著刺激内皮细胞迁移和管形成.
- 用NS-398抑制COX-2或针对血管性因素的抗体减少了癌细胞诱导的血管生成.
- 在内皮细胞中通过阿司匹林或反感性寡核酸抑制COX-1,抑制管形成,表明COX-1在内皮细胞中的独特作用.
结论:
- 结肠癌细胞中的循环氧化酶-2 (COX-2) 调节血管原因子的产生,从而促进血管生成.
- 在内皮细胞中的循环氧化酶-1 (COX-1) 直接调节血管生成,独立于癌细胞衍生因素.
- 向癌细胞中的COX-2和内皮细胞中的COX-1可能提供一种抑制瘤血管生成的双重策略.
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