α-caesalpin抑制CSPG4通路诱导胶质瘤细胞线粒体功能障碍引发凋亡的机制

α-Caesalpin Induce Mitochondrial Dysfunction in Glioma Cells through the Inhibiting of CSPG4 Pathway

胶质母细胞瘤对常规治疗耐受,寻找新的药理学靶点和有效的治疗剂,对治疗替莫唑胺抗性神经胶质瘤尤为重要。通过测定呋喃二烯酮类(α-caesalpin,α-CAE)对耐药型胶质瘤细胞的促凋亡作用和α-CAE对线粒体功能和凋亡通路的调控,研究α-CAE诱导替莫唑胺耐药的胶质瘤细胞凋亡的药理学作用和分子信号通路。研究表明α-CAE能够抑制CSPG4-AKTERK1/2通路,上调IGFBP3表达,并且引起了线粒体凋亡蛋白AIF和Bax的活化以及Drp1的募集。研究结果揭示了靶向CSPG4通路治疗化疗抵抗性胶质瘤的可能。

Glioblastoma is tolerant to conventional chemotherapy.Exploring new pharmacological targets and effective therapeutic agents is necessary for the treatment of temozolomide-resistant gliomas.In current study,the pharmacological effects and molecular signaling pathways ofα-caesalpin(α-CAE)in temozolomide-resistant glioma cells are examined through measuring the pro-apoptotic effect ofα-CAE on drug-resistant glioma cells and the regulation of mitochondrial function and apoptotic pathway byα-CAE.The results showed that,α-CAE inhibited the CSPG4-AKT-ERK1/2 pathway,up-regulated IGFBP3 expression,activated mitochondrial apoptosis proteins AIF and Bax,and recruited Drp1.This study demonstrated the possibility of treatment of chemotherapy-resistant gliomas by targeting the CSPG4 pathway.