Miyaguchi T, Nomata K, Noguchi M, Watanabe J, Satoh H, Kanetake H
Department of Urology, Nagasaki University School of Medicine, Japan.
Anticancer Res. 2001 Nov-Dec;21(6A):4025-30.
[4-3,5-Bis(trimethylsilyl)benzamido] benzoic acido] (TAC-101), which exhibits an anti-tumor effect, can bind to retinoic acid receptors (RARs). It has retinoid-like properties, such as chemopreventive action against cancer cells. The up-regulation of connexin (Cx) expression by retinoids is well known in various epithelial cells. In this study, we investigated whether TAC-101 up-regulates gap junctional intercellular communication (GJIC) in renal epithelial cells exposed to the renal carcinogens. Madin Darby canine kidney (MDCK) cells were incubated with TAC-101 for 3 days, then briefly exposed to renal carcinogens potassium bromate (KBrO3) or dimethylnitrosamine (DMN). TAC-101 increased the expression of connexin 43 protein without affecting Cx43 phosphorylation and prevented inadequate Cx43 localisation caused by KBrO3 or DMN. Consequently, TAC-101 prevented the disruption of GJIC in MDCK cells. These data suggested that TAC-101 enhanced GJIC by up-regulating Cx43 expression and that TAC-101 might be useful for the prevention of renal cell carcinoma.
[4-3,5-双（三甲基硅基）苯甲酰胺基]苯甲酸（TAC-101）具有抗肿瘤作用，它能与维甲酸受体（RARs）结合。它具有类视黄醇样特性，比如对癌细胞有化学预防作用。在各种上皮细胞中，类视黄醇上调连接蛋白（Cx）表达是众所周知的。在本研究中，我们调查了TAC-101是否能上调暴露于肾致癌物的肾上皮细胞中的间隙连接细胞间通讯（GJIC）。将Madin Darby犬肾（MDCK）细胞与TAC-101孵育3天，然后短暂暴露于肾致癌物溴酸钾（KBrO3）或二甲基亚硝胺（DMN）。TAC-101增加了连接蛋白43蛋白的表达，而不影响Cx43磷酸化，并防止了由KBrO3或DMN引起的Cx43定位不足。因此，TAC-101防止了MDCK细胞中GJIC的破坏。这些数据表明，TAC-101通过上调Cx43表达增强了GJIC，并且TAC-101可能对预防肾细胞癌有用。
