丙戊酸：诱导终末分化和衰老抑制头颈部癌症的生长。
Valproic acid: growth inhibition of head and neck cancer by induction of terminal differentiation and senescence.
机构信息
Oral Cancer Research Team, Cancer Research Initiatives Foundation, Second Floor, Outpatient Centre, Sime Darby Medical Centre, 47500 Subang Jaya, Selangor, Malaysia.
出版信息
Head Neck. 2012 Mar;34(3):344-53. doi: 10.1002/hed.21734. Epub 2011 Mar 24.
BACKGROUND
There are limited studies on the effects of drugs that modulate epigenetic regulation for head and neck squamous cell carcinoma (HNSCC). This study determined the effect of valproic acid (VPA) on HNSCC.
METHODS
Growth inhibition effects of VPA alone or in combination with 5-aza-2'deoxycytidine (5-aza-dC) or all-trans retinoic acid (ATRA) was evaluated with MTT and clonogenic assays on 5 HNSCC cell lines. The mechanism of growth inhibition was investigated by looking at markers of terminal differentiation and senescence.
RESULTS
Growth inhibition profiles of HNSCC cell lines varied in response to VPA. Inhibition of clonogenic survival in response to VPA was associated with an upregulation of p21, expression of terminal differentiation markers, and cellular senescence. Notably, a combination treatment of 5-Aza-dC-VPA-ATRA enhanced growth inhibition in cells resistant to VPA.
CONCLUSION
VPA is a potent inhibitor of proliferation in some HNSCC cell lines, and may be used to treat HNSCC.
背景
目前关于调控头颈部鳞状细胞癌（HNSCC）表观遗传调节的药物的影响的研究有限。本研究旨在确定丙戊酸（VPA）对 HNSCC 的作用。
方法
采用 MTT 和集落形成实验，评估 VPA 单独或与 5-氮杂-2'-脱氧胞苷（5-aza-dC）或全反式维甲酸（ATRA）联合使用对 5 种 HNSCC 细胞系的生长抑制作用。通过观察终末分化和衰老的标志物来研究生长抑制的机制。
结果
HNSCC 细胞系对 VPA 的生长抑制谱不同。VPA 抑制集落存活与 p21 的上调、终末分化标志物的表达和细胞衰老有关。值得注意的是，5-Aza-dC-VPA-ATRA 的联合治疗增强了对 VPA 耐药细胞的生长抑制作用。
结论
VPA 是一些 HNSCC 细胞系中增殖的有效抑制剂，可用于治疗 HNSCC。
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