Ashraf J, Kunapuli S, Chilton D, Thompson E B
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77550.
J Steroid Biochem Mol Biol. 1991 May;38(5):561-8. doi: 10.1016/0960-0760(91)90313-t.
Cortivazol is a phenylpyrazolo glucocorticoid of high potency and unusual structure. In both wild-type and highly dexamethasone(dex)-resistant clones of the human leukemic cell line CEM, exposure to cortivazol leads to cell death. It has been shown recently that in wild-type CEM cells but not in a dex-resistant, glucocorticoid receptor(GR)-defective clone ICR-27 TK-3, dex induces GR mRNA. To test the hypothesis that cortivazol acts in dex-resistant cells by making use of the residual GR found there, wild-type and dex-resistant clones were treated with various concentrations of cortivazol and induction of GR mRNA was studied. Cortivazol significantly induced GR mRNA in the normal CEM-C7 as well as in two classes of dex-resistant clones, although the dex-resistant clones needed at least 10 times more cortivazol than the normal cells for significant GR mRNA induction. Increased levels of GR mRNA were noticed as early as 3 h after treatment. A general correlation between induction of GR mRNA and lysis of the normal and dex-resistant cells was found. Positive induction of GR mRNA might be one of the earliest crucial steps in the lysis of normal and dex-resistant CEM cells, or might serve as a marker for the process. However, the lysis pathway in the dex-resistant cells is defective in that dex-resistant clones needed significantly more cortivazol than the normal cells for lysis of the cells.
可替唑是一种具有高效能和独特结构的苯基吡唑类糖皮质激素。在人白血病细胞系CEM的野生型和对地塞米松（dex）高度耐药的克隆中，暴露于可替唑都会导致细胞死亡。最近研究表明，在野生型CEM细胞中，dex可诱导GR mRNA表达，但在对地塞米松耐药、糖皮质激素受体（GR）缺陷的克隆ICR - 27 TK - 3中则不然。为了验证可替唑通过利用耐药细胞中残留的GR发挥作用这一假说，用不同浓度的可替唑处理野生型和耐药克隆，并研究GR mRNA的诱导情况。可替唑在正常CEM - C7细胞以及两类耐药克隆中均显著诱导GR mRNA表达，尽管耐药克隆诱导显著的GR mRNA表达所需的可替唑浓度至少是正常细胞的10倍。处理后3小时就可观察到GR mRNA水平升高。在正常细胞和耐药细胞的裂解与GR mRNA诱导之间发现了普遍的相关性。GR mRNA的阳性诱导可能是正常细胞和耐药CEM细胞裂解的最早关键步骤之一，或者可作为该过程的一个标志物。然而，耐药细胞的裂解途径存在缺陷，因为耐药克隆裂解细胞所需的可替唑浓度显著高于正常细胞。
