通过组蛋白去乙酰化酶抑制剂SAHA选择性诱导皮肤T细胞淋巴瘤细胞凋亡：相关的治疗作用机制

通过组蛋白去乙酰化酶抑制剂SAHA选择性诱导皮肤T细胞淋巴瘤细胞凋亡：相关的治疗作用机制
Zhang; C.; Richon; V.; Ni; X.
【期刊名称】《《世界核心医学期刊文摘：皮肤病学分册》》
【年(卷),期】2006(2)8
【摘要】Suberoylanilide hydroxamic acid (SAHA), an orally administered inhibitor of histone deacetylases, is currently in phase II clinical trials for cutaneous T cell lymphomas (CTCL), but the mechanism of SAHA action is unknown. In this study, we investigated the anti-tumor effects of SAHA in CTCL cell lines and freshly isolated peripheral blood lymphocytes (PBL)
from CTCL patients with high percentage of circulating malignant T cells. Three cell lines (MJ, Hut78, and HH) and PBL from 11 patients and three healthy donors were treated with SAHA (1, 2.5, and 5 μ M) for 24 and/or
48 h. Apoptosis was determined by flow cytometry analysis of sub- G1 hypodiploid nuclei and/or annexin V binding populations. Acetylated histones and apoptosis-associated proteins were detected by Western blotting. SAHA at 1- 5 μ M for 24 and 48 h induced apoptosis in a concentration- and time-dependent manner in three cell lines: MJ (0% - 7% and 1% - 32% ), Hut78 (4% - 36% and 5% - 54% ), and HH (4% - 67% and 8% - 81% ). SAHA at 1- 5 μ M for 48 h also induced more apoptosis of patients’ PBL than healthy donors’ (15% - 32% versus6% - 13% , p<0.05). SAHA treatment caused an accumulation of acetylated histones (H2B, H3, and
H4), an increase of p21 WAF1 and bax proteins, a decrease of Stat6 and phospho-Stat6 proteins, and activation of caspase-3 in CTCL cells. Our data suggest that selective induction of malignant T cell apoptosis and modulation of acetylated histones, p21WAF1, bax, Stat6, and caspase-3 may underlie the therapeutic action of SAHA in CTCL patients.
【总页数】2页(P22-23)
【作者】Zhang; C.; Richon; V.; Ni; X.
【作者单位】Department; of; Dermatology; Box; 434; U.; T.; M.; D.; Anderson; Cancer; Center; 1515; Hotcombe; Boulevard; Houston; TX; 77030; United; States-J.; INVEST.; DERMATOL.; 2005; 125/5; （1045-1052）; 不详【正文语种】中文
【中图分类】R733.7
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