Differentiation of rhabdomyosarcoma cell lines using retinoic acid
Differentiation of rhabdomyosarcoma cell lines using retinoic acid
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DOI：
10.1002/pbc.20650
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发表时间：
2006-11-01
影响因子：
3.2
通讯作者：
Malkin, David
中科院分区：
文献类型：
--
作者：
Barlow, Jason W.;Wiley, Joe C.;Malkin, David
横纹肌肉瘤（Rhabdomyosarcoma， RMS）是儿童和青少年最常见的散发性软组织肉瘤。通过手术、放疗和化疗，RMS患者的总体5年生存率为70%。需要新的治疗方法来改善这些结果，特别是对于更具侵袭性的肺泡性RMS （ARMS）和疾病晚期，其5年生存率低于20%。类维生素a已成功用于治疗急性早幼粒细胞白血病（APML）和神经母细胞瘤。目的。然而，类维生素a作为RMS的鉴别剂的分析还不完整。本研究通过检测五种RMS细胞系对全反式维甲酸（ATRA）或9-顺式维甲酸（CRA）的肌原性蛋白表达，研究了维甲酸（RA）促进RMS细胞系分化的能力。结果。生长曲线分析表明，两种类维生素a均抑制Rh4和Rh28的细胞生长。RD细胞仅对cra有应答，而Rh30和Rh18无应答。在ATRA治疗后，FACS分析显示细胞周期的改变与生长曲线的模式相同。ATRA改变了两种细胞系Rh4和Rh28的细胞形态，并诱导了这些细胞中肌钙蛋白T的表达，表明其具有分化作用。结论。这些研究表明，类维生素a是一些RMS细胞系生长停滞和分化的有效诱导剂，为进一步在小鼠体内测试ATRA作为治疗ARMS的潜在方法提供了基础。
Background Rhabdomyosarcoma (RMS) is the most frequent sporadic soft tissue sarcoma of childhood and adolescence. The overall 5-year survival rate for patients with RMS is 70% with the use of surgery, radiation, and chemotherapy. Novel therapeutic approaches are necessary to improve on these outcomes particularly among the more aggressive alveolar RMS (ARMS) and late stages of disease, where 5-year survival is less than 20%. Retinoids have been successfully used in the treatment of acute promyelocytic leukemia (APML) and neuroblastoma. Purpose. However, analysis of retinoids as a differentiating agent for RMS has been incomplete. This work examined the ability of retinoic acid (RA) to promote differentiation of RMS cell lines by examining the expression of myogenic proteins in five RMS cell lines in response to All-Trans Retinoic Acid (ATRA) or 9-cis retinoic acid (CRA). Results. Analysis of growth curves indicates that both retinoids suppress cell growth of Rh4 and Rh28. RD cells only responded to-CRA whereas Rh30 and Rh18 did not respond. Following treatment with ATRA FACS analysis showed an altered cell cycle with the same pattern as the growth curves. ATRA altered cellular morphology of two cell lines, Rh4 and Rh28, and induced Troponin T expression in these cells suggesting a differentiating effect. Conclusions. These studies suggest that retinoids are effective inducers of growth arrest and differentiation in some RMS cell lines, and offer a basis for further in vivo testing in mice of ATRA as a potential approach to ARMS treatment.