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作 者:游飘雪 陈兰 施艺玮 王辉 晁亮 洪战英[1,2] YOU Piaoxue;CHEN Lan;SHI Yiwei;WANG Hui;CHAO Liang;HONG Zhanying(School of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;School of Pharmacy,Naval Medical University,Shanghai 200433,China)
机构地区:[1]福建中医药大学药学院,福建福州350122 [2]海军军医大学药学系,上海200433
出 处:《药学实践与服务》2025年第2期59-66,共8页Journal of Pharmaceutical Practice and Service
基 金:国家自然科学基金项目(82173777,81872829)。
摘 要:目的构建一种脑胶质瘤微流控芯片模型,模拟肿瘤微环境,用于抗脑胶质瘤中药药效评价。方法将神经胶质细胞瘤细胞U251接种于不同培养方式的微流控芯片内,对所构建的模型内细胞的活力和肿瘤微环境进行表征,采用荧光染色法评价阳性药替莫唑胺(TMZ)和多西他赛(DOC)对模型内细胞活性和凋亡的影响,将该模型应用于中药半枝莲提取液抗脑胶质瘤的药效评价。结果所构建的U251微流控芯片模型中细胞具有较高活力,并能够在一定程度上模拟肿瘤缺氧的微环境;芯片中U251细胞的活力随着阳性药浓度的升高而降低,3D培养的U251细胞活力高于2D培养(P<0.05);细胞内线粒体膜电位随着阳性药浓度的升高而下降;2 mg/ml半枝莲提取液可以一定程度上杀伤U251细胞,并可以降低模型内细胞的线粒体膜电位。结论成功构建了能有效模拟肿瘤微环境和快速评估抗肿瘤药效的脑胶质瘤微流控芯片模型,为抗脑胶质瘤中药的药效评价和活性成分筛选提供了新策略。Objective To construct a glioma microfluidic chip model to simulate tumor microenvironment for evaluating the medicinal efficacy of anti-glioma traditional Chinese medicines.Methods Glioblastoma cells U251 were seeded into microfluidic chips with different culture modes,and the cell viability and tumour microenvironment within the constructed model were characterized.Fluorescence staining was used to evaluate the effects of the positive drugs temozolomide(TMZ)and docetaxel(DOC)on the cell activity and apoptosis within the model,which was applied to evaluate the medicinal efficacy of the extracts of the herb Scutellaria barbata on gliomas.Results The cells in the constructed U251 microfluidic chip model displayed high viability and were able to mimic the hypoxic microenvironment of tumor to a certain extent.The viability of the U251 cells in the microfluidic chips decreased with the increasing of the concentration of the positive drug,and the viability of the 3D cultured U251 cells was higher than that in the 2D condition(P<0.05).The intracellular mitochondrial membrane potential decreased with the increasing of the concentration of the positive drug.And the 2 mg/ml Scutellaria barbata extract killed U251 cells to a certain extent and reduced the mitochondrial membrane potential of the cells in the model.Conclusion This study successfully constructed a microfluidic chip model of glioma that could effectively simulate the tumor microenvironment and rapidly evaluate the anti-tumor medicinal efficacy,which provided a new strategy for the medicinal efficacy evaluation and active components screening of antiglioma traditional Chinese medicines.
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