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贝伐单抗联合多西环素治疗胶质瘤的疗效与机制研究
黄培成,程小耕,杨强,毕敬涛,曹姗姗
0
(绵阳市中心医院药学部;北京积水潭医院;北京出入境检验检疫局)
摘要:
【摘要】 目的 探讨贝伐单抗联合多西环素治疗胶质瘤的疗效与相关机制。方法〓以胶质瘤原代细胞为模型,分别用生理盐水、贝伐单抗和贝伐单抗联合多西环素处理胶质瘤细胞,并分为生理盐水组、贝伐单抗组和贝伐单抗联合多西环素组。采用MTS法及克隆形成实验检测各处理组细胞的增殖情况;同时利用划痕及Transwell侵袭实验,检测不同处理组细胞的迁移及侵袭能力,并在裸鼠皮下注射胶质瘤原代细胞,15天后分别用生理盐水、贝伐单抗和贝伐单抗联合多西环素进行治疗处理,观察移植瘤大小、重量差异,并进一步通过免疫组化法验证各组移植瘤中CD34及Ki67的差异。 结果〓贝伐单抗组细胞增殖和克隆形成能力、迁移和侵袭能力明显低于生理盐水组(P<005),而贝伐单抗联合多西环素组抑制效果更显著且与贝伐单抗组比较,差异有统计学意义(P<005);贝伐单抗组处理后移植瘤的大小、重量和体积均抑制明显,与生理盐水组比较差异有统计学意义(P<005),而贝伐单抗联合多西环素组抑制更为明显,与贝伐单抗组比较,差异均有统计学意义(P<001);贝伐单抗组的CD34及Ki67表达较生理盐水组下降(P<001),贝伐单抗联合多西环素组下降更明显,与贝伐单抗组比较,差异均有统计学意义(P<001)。结论〓贝伐单抗联合多西环素治疗胶质瘤,通过抑制细胞增殖、迁移和侵袭能力,药物产生叠加效应显著增强抗肿瘤作用,可减少肿瘤新生血管的形成,从而抑制胶质瘤的生长、重量和体积,为临床治疗胶质瘤提供了理论依据。
关键词:  胶质瘤  贝伐单抗  多西环素  联合治疗
DOI:
基金项目:国家“十三五”重点研发计划项目
Efficacy and mechanism study of bevacizumab combined with doxycycline in the treatment of gliomas
HUANG Peicheng,CHENG Xiaogeng,YANG Qiang,BI Jingtao,CAO Shanshan
(Department of Pharmacy, Mianyang Central Hospital;Beijing Jishuitan Hospital;Beijing EntryExit Inspection and Quarantine Bureau)
Abstract:
【Abstract】 Objective To study the efficacy of bevacizumab combined with doxycycline in the treatment of glioma. Methods〓Glioma primary cells as a model, were treated by normal saline, bevacizumab and bevacizumab combined with doxycycline. MTS method and clone formation assay were used to detect the proliferation of cells in each treatment group. Scratch assay and transwell method were used to detect the invasion ability of cells in different treatment groups; At last, we injected primary glioma cells into subcutaneous of nude mice, addednormal saline, bevacizuma and bevacizumab combined with doxycycline for treatment after injected 15 days, and then observed the different size of transplant tumor and verified the different expression of CD34 and Ki67 in transplant tumor by immunohistochemistry. Results〓Compared with the normal saline group, the cells ability of colony formation, migration and invasion were weakened by bevacizumab treatment (P<005), but bevacizumab combined with doxycycline treatment weakened effect is more obvious (P<001); Then, compared with the normal saline group, the volume of the xenografts after bevacizumab treatment became smaller (P<005), but the volume of the xenografts treated with bevacizumab combined with doxycycline was smallest (P<001). Immunohistochemistry results showed that bevacizumab treatment group had a downregulation of CD34 and Ki67 relative to the normal saline group, even the bevacizumab combined with doxycycline treatment effect is more obvious. Conclusion〓Bevacizumab combined with doxycycline treatment of glioma has a certain effect.
Key words:  Gliomas  Bevacizumab  Doxycycline  Combination therapy

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