Chiantore M V, Giandomenico V, De Luca L M
Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20892-4255, USA.
Biochem Biophys Res Commun. 1999 Jan 27;254(3):636-41. doi: 10.1006/bbrc.1998.9987.
Retinoic acid (RA)-resistant cell lines are highly malignant. To inhibit the growth of the RA-resistant cells we used 4-HPR, a synthetic retinoid, which may act through alternative signal transduction pathways. 4-HPR induced cell growth inhibition and apoptosis in all RA-sensitive as well as -resistant cells, demonstrating a wider spectrum of potency over RA. 4-HPR induced tissue TGase activity. A tight correlation between the induction of tissue TGase, the inhibition of cell growth, and apoptosis was evident in all eight RA-sensitive cell lines. However, basal TGase differed in the different cells, suggesting inducibility rather than basal levels as the relevant parameter. In sharp contrast to the RA-sensitive cells, RA-resistant cells showed sporadic response to 4-HPR for tissue TGase. The wider spectrum of activity of 4-HPR in inhibiting cell growth and inducing apoptosis makes it a good candidate for the treatment of RA-resistant cancer cells.
维甲酸（RA）耐药细胞系具有高度恶性。为了抑制RA耐药细胞的生长，我们使用了4-羟基苯基视黄酸（4-HPR），一种合成类视黄醇，它可能通过替代信号转导途径发挥作用。4-HPR在所有RA敏感以及耐药细胞中均诱导细胞生长抑制和凋亡，表明其效力谱比RA更广泛。4-HPR诱导组织转谷氨酰胺酶（TGase）活性。在所有八个RA敏感细胞系中，组织TGase的诱导、细胞生长的抑制和凋亡之间存在紧密的相关性。然而，不同细胞中的基础TGase有所不同，这表明诱导性而非基础水平是相关参数。与RA敏感细胞形成鲜明对比的是，RA耐药细胞对4-HPR诱导的组织TGase表现出零星反应。4-HPR在抑制细胞生长和诱导凋亡方面更广泛的活性谱使其成为治疗RA耐药癌细胞的良好候选药物。
