Inhibitory effects of 9-cis-retinoic acid and pyrrolidinedithiocarbamate on cyclooxygenase (COX)-2 expression and cell growth in human skin squamous carcinoma cells
Inhibitory effects of 9-cis-retinoic acid and pyrrolidinedithiocarbamate on cyclooxygenase (COX)-2 expression and cell growth in human skin squamous carcinoma cells
复制标题
DOI：
10.1016/s0304-3835(00)00604-2
复制
发表时间：
2000-12-20
期刊：
影响因子：
9.7
通讯作者：
Kanzaki, T
中科院分区：
文献类型：
--
作者：
Kanekura, T;Higashi, Y;Kanzaki, T
我们最近发现，在人皮肤表皮癌细胞中，环氧合酶（考克斯）-2蛋白的组成性表达和前列腺素E-2（PGE（2））的生物合成显著增强，并且通过转染考克斯-2反义寡核苷酸抑制考克斯-2表达，癌细胞生长被有效地抑制。本研究的目的是寻找抑制考克斯-2表达的药物，并检查它们对细胞生长的影响。由于类维生素A和抗氧化剂已被用于化学预防癌症在几个组织中，这些药物对考克斯-2的表达和PGE？研究了皮肤鳞状细胞癌细胞中的生物合成。用类维生素A（9-cis-RA）或抗氧化剂（吡咯烷二硫代氨基甲酸酯（PDTC））处理以浓度依赖性方式抑制考克斯-2表达和PGE 2生物合成。9-cis-RA和PDTC对细胞生长有明显的抑制作用。结果提示9-cis-RA和PDTC可能对皮肤癌的发生有一定的预防作用，而考克斯-2可能参与了它们对皮肤癌的预防作用。(C)2000爱思唯尔科学爱尔兰有限公司保留所有权利。
We recently demonstrated that the constitutive expression of cyclooxygenase (COX)-2 protein and prostaglandin E-2 (PGE(2)) biosynthesis were significantly enhanced in human skin epidermal cancer cells and that cancer cell growth was effectively inhibited by the suppression of COX-2 expression by transfection with COX-2 antisense oligonucleotide. The purpose of this study was to search for agents which suppress COX-2 expression and examine their effects on cell growth. Since retinoids and antioxidants have been used for chemoprevention of cancers in several tissues, the effects of these agents on COX-2 expression and PGE? biosynthesis in skin squamous carcinoma cells were investigated. Treatment with a retinoid (9-cis-retinoic acid (9-cis-RA)) or an antioxidant (pyrrolidinedithiocarbamate (PDTC)) suppressed COX-2 expression and PGE2 biosynthesis in a concentration-dependent manner. Cell growth was significantly inhibited by 9-cis-RA and PDTC. These results suggest that 9-cis-RA and PDTC may be useful in preventing skin cancer grow;th and that COX-2 is involved in their protective effects on skin carcinogenesis. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.