Oguro T, Liu J, Klaassen C D, Yoshida T
Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Toxicol Sci. 1998 Sep;45(1):88-93. doi: 10.1006/toxs.1998.2485.
Oleanolic acid (OA) has been shown to inhibit mouse skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA). This study was designed to examine the effect of OA on the TPA-induced expression of the ornithine decarboxylase (ODC) gene as well as other genes. OA inhibited the induction of ODC activity and mRNA level produced by TPA in the skin of female CD-1 mice. Preapplication of OA (10 mumol) to the mouse dorsal skin produced an approximately 50% decrease in TPA (8 nmol)-induced epidermal ODC activity, as well as ODC gene expression. These results suggest that OA inhibits TPA-induced ODC mainly at the transcriptional level. In addition to ODC, TPA also stimulated metallothionein (MT) gene expression in mouse skin. A dose of 2.5 mumol of OA diminished the TPA-induced MT mRNA 50%. Treatment with OA (10 mumol) after TPA (8 nmol) application also inhibited ODC and MT gene expression which suggests that OA does not compete with TPA for its receptor. OA pretreatment also prevented c-fos gene expression. All of these findings suggest that OA diminishes some signal transduction pathways of TPA to suppress target gene expression in mouse skin. This study suggests that OA might be a general inhibitor against TPA-stimulated gene expression in mouse skin.
齐墩果酸（OA）已被证明可抑制12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）诱导的小鼠皮肤肿瘤促进作用。本研究旨在检测OA对TPA诱导的鸟氨酸脱羧酶（ODC）基因以及其他基因表达的影响。OA抑制了TPA在雌性CD - 1小鼠皮肤中诱导产生的ODC活性和mRNA水平。在小鼠背部皮肤预先涂抹OA（10 μmol），可使TPA（8 nmol）诱导的表皮ODC活性以及ODC基因表达降低约50%。这些结果表明，OA主要在转录水平抑制TPA诱导的ODC。除了ODC，TPA还刺激了小鼠皮肤中金属硫蛋白（MT）基因的表达。2.5 μmol的OA剂量可使TPA诱导的MT mRNA减少50%。在涂抹TPA（8 nmol）后用OA（10 μmol）处理也抑制了ODC和MT基因表达，这表明OA不与TPA竞争其受体。OA预处理还可防止c - fos基因表达。所有这些发现表明，OA可减少TPA的一些信号转导途径，以抑制小鼠皮肤中的靶基因表达。本研究表明，OA可能是一种针对TPA刺激的小鼠皮肤基因表达的通用抑制剂。
