柴胡皂苷D对阿霉素治疗小鼠肝癌的靶向导引作用  

Guiding role of saikosaponin D in targeted therapy of doxorubicin on mouse liver cancer

作　　者：许严伟 耿胜男 王梦琪 杜钢军 XU Yan-wei;GENG Sheng-nan;WANG Meng-qi;DU Gang-jun(Zhengzhou University of Industrial Technology,Zhengzhou 451150,China;Luoyang Third People’s Hospital,Luoyang 471000,China;Pharmaceutic College of Henan University,Kaifeng 475000,China)

机构地区：[1]郑州工业应用技术学院,河南郑州451150 [2]洛阳市第三人民医院,河南洛阳471000 [3]河南大学药学院,河南开封475000

出　　处：《中草药》2021年第3期778-788,共11页Chinese Traditional and Herbal Drugs

基　　金：河南省自然科学基金资助项目(182300410310);郑州工业应用技术学院校级科研项目(2018YB021);洛阳市医疗卫生科技计划项目(1980002A)。

摘　　要：目的探讨柴胡皂苷D对阿霉素治疗小鼠肝癌可能的靶向导引作用。方法以小鼠肝癌H_(22)实体瘤模型评价柴胡皂苷D与阿霉素单独或联合对荷瘤小鼠的治疗效果。噻唑蓝(methyl thiazolyl tetrazolium,MTT)检测细胞增殖情况,激光全息系统分析细胞大小,2′,7′-二氯荧光黄双乙酸盐(2′,7′-dichlorodi-hydrofluoresceindiacetate,DCFH-DA)检测细胞活性氧(reactive oxygen species,ROS)水平,线粒体示踪绿检测细胞线粒体功能,吖啶橙(acridine orange,AO)染色检测细胞自噬情况,Western blotting印迹法检测细胞有机阴离子转运多肽(organic aniontransporting polypeptide 1B1,Oatp1b1)的表达情况。结果0.5~16μg/m L柴胡皂苷D不影响H_(22)细胞增殖,但能增加H_(22)细胞体积,促进细胞摄取阿霉素,增强阿霉素的细胞增殖抑制作用。柴胡皂苷D能降低H_(22)细胞ROS水平,促进细胞线粒体功能和细胞自噬,增加细胞Oatp1b1的表达。柴胡皂苷D在20 mg/kg对小鼠肝癌H_(22)皮下实体瘤生长无影响,增加瘤组织阿霉素摄取,提高阿霉素对肝肿瘤的治疗效果。柴胡皂苷D可改善瘤组织细胞外基质沉积,降低转化生长因子-β1(transforming growth factor-β1,TGF-β1)水平和血管通透性。结论柴胡皂苷D对阿霉素治疗小鼠肝癌有靶向导引作用,其机制是促进细胞自噬及线粒体功能,继而促进Oatp1b1表达,减少细胞外基质沉积。Objective To observe whether saikosaponin D has the guiding role in targeted therapy of doxorubicin for mouse liver cancer and explore its guiding mechanism of targeted therapy.Methods H_(22)mouse liver solid tumor model was used to evaluate the therapeutic efficacy of saikosaponin D and doxorubicin alone or in combination on tumor-bearing mice.Cell proliferation was examined by MTT assay.Cell size was analyzed by laser holographic analysis system,cell reactive oxygen species(ROS)was tested by DCFH-DA,Mito-Tracker Green was used to examine mitochondrial function,AO staining was used to test cell autophagy,and cell Oatp1 b1 expression was examined by Western blotting.Results Saikosaponin D at the experimental concentrations of 0.5—16μg/m L had no effect on H_(22)cell proliferation,but could increase H_(22)cell volume,promote cell to uptake doxorubicin and enhance the inhibitory action of doxorubicin on cell proliferation.Saikosaponin D could reduce ROS level of H_(22)cell,promote cell mitochondrial function and cell autophagy,and increased cell Oatp1 b1 expression.Saikosaponin D at the experimental doses of 20 mg/kg had no effect on subcutaneous solid tumors in H_(22)liver cancer-bearing mice,could increase doxorubicin uptake in tumor tissues and the therapeutic efficacy of doxorubicin on liver tumors.Saikosaponin D could improve the extracellular matrix deposition in tumor tissues,decrease TGF-β1 and vessel permeability.Conclusion Saikosaponin D had the guiding role in targeted therapy of doxorubicin for mouse liver cancer,its guiding mechanism was to maintain cell autophagy and mitochondrial function,then to promote Oatp1 b1 expression and reduce extracellular matrix deposition.

关 键 词：柴胡皂苷D 阿霉素 肝癌H22细胞 导引作用 靶向治疗 

分 类 号：R285[医药卫生—中药学]