声动力疗法联合高热疗法诱导胶质瘤细胞凋亡  

Apoptosis of human glioma cells induced by the combination of 5-aminolevulinic acid-mediated sonodynamic therapy and hyperthermotherapy

作　　者：武宏杰[1] 鞠东辉 李波 张伟光[2] 段兴邦[2] 陈会荣 Wu Hongjie;Ju Donghui;Li Bo;Zhang Weiguang;Duan Xingbang;Chen Huirong(Department of Neurosurgery,the First Affiliated Hospital of Henan University of Science and Technology,Luoyang,Henan 471000,China;Department of Neurosurgery,the Fourth Affiliated Hospital of Harbin Medical University,Harbin,Heilongjiang 150001,China;Department of Neurosurgery,First People's Hospital of Taizhou,Taizhou,Zhejiang 318020,China)

机构地区：[1]河南科技大学第一附属医院神经外科,河南洛阳471000 [2]哈尔滨医科大学附属第四医院神经外科,黑龙江哈尔滨150001 [3]台州市第一人民医院神经外科,浙江台州318020

出　　处：《中国微侵袭神经外科杂志》2024年第1期19-23,共5页Chinese Journal of Minimally Invasive Neurosurgery

基　　金：黑龙江省博士后科学基金(编号:LBH-Q20140)。

摘　　要：目的探讨声动力疗法(sonodynamic therapy,SDT)联合高热疗法(hyperthermotherapy,HT)的抗胶质瘤作用及可能机制。方法体外培养胶质瘤细胞株SNB19、U87MG,分为对照组、HT组、SDT组与SDT+HT组。应用阿尔玛蓝实验评估肿瘤细胞增殖能力,流式细胞术分析细胞凋亡率、线粒体膜电位和细胞内活性氧生成,Western blot法检测细胞凋亡相关蛋白表达情况。结果与SDT组比较,SDT+HT组抑制胶质瘤细胞增殖,与5-氨基乙酰丙酸(5-ALA)浓度、超声照射时间和HT温度呈正相关(均P<0.05),并伴随细胞活力下降的典型形态学变化。较低剂量HT(42℃作用15min)可明显促进SDT介导细胞内活性氧生成增多,线粒体膜电位水平下降和细胞凋亡增加(均P<0.05)。与对照组、HT组、SDT组比较,SDT+HT组上调cleaved caspase-3、-8、-9和Bax蛋白表达,下调Bcl-2蛋白表达(均P<0.05)。结论HT能够显著促进5-ALA-SDT抑制细胞增殖、诱导细胞凋亡,进而抑制胶质瘤生长。SDT联合HT疗法是一个颇具潜力的胶质瘤治疗方法。Objective To investigate the anti-glioma effects and possible mechanisms of action of sonodynamic therapy(SDT)combined with hyperthermia(HT).Methods The human glioma cell lines SNB19 and U87MG were cultured in vitro and divided into control group,HT group,SDT group and SDT+HT group.Alamar blue assay was performed to assess the inhibiting effect on the proliferation of glioma cells.Apoptotic rate,mitochondrial membrane potential and reactive oxygen species(ROS)were examined by flow cytometer.The effect of SDT+HT on the expression of apoptosis-related proteins,including cleaved caspase-3,-8,and-9,Bax and Bcl-2,was detected with Western blot.Results Compared with SDT group,the SDT+HT group inhibited glioma cell proliferation,which was positively correlated with 5-aminolevulinic acid(5-ALA)concentration,ultrasound exposure time and HT temperature(all P<0.05),and was accompanied by typical morphological changes of decreased cell viability.Lower dose of HT(42°C for 15 min)significantly promoted the increase of SDT-mediated intracellular ROS production,the decrease of mitochondrial membrane potential level and the increase of apoptosis(all P<0.05).Compared with the control group,HT group and SDT group,the SDT+HT group up-regulated the protein expression of cleaved caspase-3,-8,-9 and Bax,and down-regulated the expression of Bcl-2 protein(all P<0.05).Conclusions HT may significantly facilitate 5-ALA-SDT to inhibit glioma cell proliferation and induce apoptosis,and then inhibit glioma growth.SDT combined with HT therapy is a promising treatment for glioma.

关 键 词：神经胶质瘤 声动力疗法 高热疗法 细胞凋亡 

分 类 号：R730.264[医药卫生—肿瘤]