Cinatl J, Cinatl J, Scholz M, Driever P H, Henrich D, Kabickova H, Vogel J U, Doerr H W, Kornhuber B
Zentrum der Hygiene, Abteilung Medizinische Virologie, Zentrum der Kinderheilkunde und Jugendmedizin, Frankfurt, Germany.
Anticancer Drugs. 1996 Sep;7(7):766-73. doi: 10.1097/00001813-199609000-00008.
Valproic acid (VPA) is a simple branched-chain fatty acid that has anticonvulsant activity and is widely used in the treatment of epilepsy. VPA was found to effect growth and differentiation of human neuroblastoma (NB) cells in vitro at concentrations that have been achieved in humans with no significant adverse effects. Treatment of UKF-NB-2 and UKF-NB-3 NB cell lines with VPA at concentrations ranging from 0.5 to 2 mM resulted in neuronal morphological differentiation characterized by extension of cellular processes without significant effects on cell viability. Ultrastructural features of VPA-treated cells were consistent with the neuronal type of differentiation. VPA treatment of NB cells was associated with decreased expression of N-myc oncoprotein and increased expression of neural cell adhesion molecule in their membrane. Treatment of NB cells with 0.5 mM VPA increased their sensitivity to lymphokine-activated killer lysis. The results indicate that VPA, at non-toxic pharmacological concentrations, arrests the growth, induces differentiation and increases immunogenicity of NB cells through non-toxic mechanisms.
丙戊酸（VPA）是一种简单的支链脂肪酸，具有抗惊厥活性，广泛用于治疗癫痫。研究发现，丙戊酸在人体中达到的浓度下可在体外影响人神经母细胞瘤（NB）细胞的生长和分化，且无明显不良反应。用浓度范围为0.5至2 mM的丙戊酸处理UKF-NB-2和UKF-NB-3 NB细胞系，可导致神经元形态分化，其特征为细胞突起延长，且对细胞活力无显著影响。丙戊酸处理细胞的超微结构特征与神经元类型的分化一致。丙戊酸处理NB细胞与膜中N-myc癌蛋白表达降低和神经细胞粘附分子表达增加有关。用0.5 mM丙戊酸处理NB细胞可增加其对淋巴因子激活的杀伤细胞裂解的敏感性。结果表明，在无毒的药理浓度下，丙戊酸通过无毒机制抑制NB细胞生长、诱导分化并增加其免疫原性。
