丙戊酸抗胶质瘤的作用机制研究进展  

Research progress on the mechanism of valproic acid against glioma

作　　者：张淑贤 朱坤 刘双萍 ZHANG Shuxian;ZHU Kun;LIU Shuangping(School of Medicine,Dalian University,Liaoning Dalian 116622,China)

机构地区：[1]大连大学医学院,辽宁大连116622

出　　处：《中国药房》2023年第10期1276-1280,共5页China Pharmacy

基　　金：辽宁省高等学校创新人才基金(No.辽教函[2020]389号)。

摘　　要：胶质瘤是中枢神经系统常见的原发性肿瘤。常规治疗方法是手术切除结合放化疗,但常常预后不良。因此,迫切需要在胶质瘤中识别新的潜在靶点并开发更有效的治疗药物。丙戊酸具有组蛋白去乙酰化酶抑制剂性质,已被证实对多种肿瘤有抑制作用。现有研究证实,丙戊酸可通过调控细胞外信号调节激酶/蛋白激酶B(Akt)信号通路、Akt/哺乳动物雷帕霉素靶蛋白等信号通路,以及调节回复引导半胱氨酸丰富蛋白Kazal基元、O^(6)-甲基鸟嘌呤DNA甲基转移酶、核转录因子红系2相关因子2、对氧磷酶2、Smad4、糖原合成酶激酶-3β等蛋白表达水平,进而诱导胶质瘤细胞凋亡和细胞周期阻滞,降低胶质瘤细胞侵袭转移能力,增加胶质瘤细胞放化疗敏感性等多种途径发挥抗肿瘤作用。此外,丙戊酸还可通过抑制胶质瘤干细胞的生长和诱导胶质瘤干细胞的分化提高抗癌药物效果。总之,丙戊酸可通过多靶点作用方式抑制胶质瘤,有可能成为治疗胶质瘤的新型靶向药物。Gliomas are commonly central nervous system tumors.The conventional treatment is surgical resection combined with chemoradiotherapy,but glioma patients often have a poor prognosis.Therefore,there is an urgent need to identify new potential targets in gliomas and develop more effective treatments.Valproic acid has the properties of histone deacetylase inhibitor,which has been proven to have inhibitory effects on various tumors.It is confirmed that valproic acid could promote apoptosis and cell arrest of glioma cells,inhibit cell invasion and glioma stem cells,increase the sensitivity of glioma cells to radiotherapy and chemotherapy by regulating ERK/Akt signaling pathway,Akt/mTOR signaling pathway,and regulating expression levels of RECK,MGMT,Nrf2,PON2,Smad4,GSK3βand other proteins.In addition,valproic acid can also enhance the effectiveness of anticancer drugs by inhibiting the growth of glioma stem cells and inducing their differentiation.In conclusion,valproic acid can inhibit glioma through multiple targeted actions,and may become a new targeted drug for the treatment of glioma.

关 键 词：丙戊酸 胶质瘤 细胞凋亡 组蛋白去乙酰化酶抑制剂 

分 类 号：R96[医药卫生—药理学] R739.4[医药卫生—药学]