Coffey D C, Kutko M C, Glick R D, Butler L M, Heller G, Rifkind R A, Marks P A, Richon V M, La Quaglia M P
Department of Pediatrics, Joan and Sanford I. Weill Graduate School of Medical Sciences of Cornell University, New York, New York, USA.
Cancer Res. 2001 May 1;61(9):3591-4.
Histone deacetylase inhibitors (HDACIs) inhibit the growth of a variety of transformed cells in culture. We demonstrated previously that the hybrid-polar HDACI m-carboxycinnamic acid bis-hydroxamide (CBHA) induces apoptosis of human neuroblastoma in vitro and is effective in lower doses when combined with retinoids. The current study investigates the effect of CBHA on the growth of human neuroblastoma in vivo, both alone and in combination with all-trans retinoic acid (atRA), using a severe combined immunodeficiency-mouse xenograft model. CBHA (50, 100, and 200 mg/kg/day) inhibited growth of SMS-KCN-69n tumor xenografts in a dose-dependent fashion, with 200 mg/kg CBHA resulting in a complete suppression of tumor growth. The efficacy of 50 and 100 mg/kg CBHA was enhanced by the addition of 2.5 mg/kg atRA. This dose of atRA was ineffective when administered alone. Treatment was accompanied by mild weight loss in all groups except the lowest dose of CBHA. Our results suggest HDACIs alone or combined with retinoids may have therapeutic utility for neuroblastoma.
组蛋白去乙酰化酶抑制剂（HDACIs）可抑制培养的多种转化细胞的生长。我们之前证明，杂合极性HDACI间羧基肉桂酸双羟肟酸（CBHA）在体外可诱导人神经母细胞瘤凋亡，并且与视黄酸联合使用时，在较低剂量下也有效。本研究使用严重联合免疫缺陷小鼠异种移植模型，研究了CBHA单独以及与全反式维甲酸（atRA）联合使用时对人神经母细胞瘤体内生长的影响。CBHA（50、100和200毫克/千克/天）以剂量依赖性方式抑制SMS-KCN-69n肿瘤异种移植的生长，200毫克/千克CBHA可完全抑制肿瘤生长。添加2.5毫克/千克atRA可增强50和100毫克/千克CBHA的疗效。该剂量的atRA单独给药时无效。除最低剂量的CBHA组外，所有组的治疗均伴有轻度体重减轻。我们的结果表明，HDACIs单独或与视黄酸联合使用可能对神经母细胞瘤具有治疗作用。
