Kargman S L, O'Neill G P, Vickers P J, Evans J F, Mancini J A, Jothy S
Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research, Quebec, Canada.
Cancer Res. 1995 Jun 15;55(12):2556-9.
Prostaglandin G/H synthase (PGHS), a key enzyme leading to the formation of prostaglandins, is the target of nonsteroidal antiinflammatory drugs. Two forms of the enzyme have been identified, PGHS-1 and PGHS-2. Epidemiological evidence has suggested that aspirin and other nonsteroidal antiinflammatory drugs may reduce the risk of colorectal cancer. We examined by immunoblot analyses the expression of human PGHS-1 and PGHS-2 protein in 25 matched colon cancer and nontumor tissues, 4 premalignant polyps, 5 control colon tissues from noncancer patients, and 3 matched normal and cancerous breast tissue samples. PGHS-1 was detected in all normal and tumor tissue. In contrast, PGHS-2 was not detected in 23 of 25 normal colon tissues but was detected in 19 of 25 colon tumors. PGHS-2 protein was not observed in four human premalignant polyp samples, control colon from noncancer patients, or matched normal or cancerous breast tissues. These results suggest that the beneficial effects of nonsteroidal antiinflammatory drugs in colon cancer may be mediated by inhibition of PGHS-2.
前列腺素G/H合酶（PGHS）是导致前列腺素形成的关键酶，是非甾体抗炎药的作用靶点。该酶已被鉴定出两种形式，即PGHS-1和PGHS-2。流行病学证据表明，阿司匹林和其他非甾体抗炎药可能会降低患结直肠癌的风险。我们通过免疫印迹分析检测了25对匹配的结肠癌组织和非肿瘤组织、4个癌前息肉、5个来自非癌症患者的对照结肠组织以及3对匹配的正常和癌性乳腺组织样本中人类PGHS-1和PGHS-2蛋白的表达。在所有正常组织和肿瘤组织中均检测到PGHS-1。相比之下，在25个正常结肠组织中的23个中未检测到PGHS-2，但在25个结肠肿瘤中的19个中检测到了PGHS-2。在4个人类癌前息肉样本、非癌症患者的对照结肠组织或匹配的正常或癌性乳腺组织中未观察到PGHS-2蛋白。这些结果表明，非甾体抗炎药对结肠癌的有益作用可能是通过抑制PGHS-2来介导的。
