桔梗皂苷D对阿霉素治疗小鼠肺癌的导引机制  

Guiding mechanism of platycodin D in treatment of mouse lung cancer with doxorubicin

作　　者：许严伟 耿胜男 王越华 杜钢军 XU Yan-wei;GENG Sheng-nan;WANG Yue-hua;DU Gang-jun(Zhengzhou University of Industrial Technology,Xinzheng 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,河南新郑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：《中国中药杂志》2021年第6期1480-1489,共10页China Journal of Chinese Materia Medica

基　　金：河南省自然科学基金项目(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：观察桔梗皂苷D是否对阿霉素治疗小鼠肺癌有导引作用。体外桔梗皂苷D与阿霉素单独或联合加入小鼠Lewis肺癌(LLC)细胞,检测细胞增殖和对阿霉素的摄取;细胞全息分析系统分析细胞形态变化,荧光黄示踪法检测细胞缝隙连接通讯功能,溶酶体示踪红检测细胞溶酶体功能,LC-3B(light chain 3 beta)和P62(heat shock 90-like protein)染色法检测细胞自噬和自噬降解,Western blot法检测细胞P-糖蛋白(P-glycoprotein, P-gp)的表达。体内将小鼠LLC细胞经尾静脉注射接种形成肺实体瘤,桔梗皂苷D与阿霉素单独或联合治疗4周,检测肿瘤大小,记录小鼠存活时间,检测肺组织对阿霉素的摄取,并对肺组织进行HE(hematoxylin-eosin)染色和免疫组化染色。结果显示,桔梗皂苷D在实验浓度不影响LLC细胞增殖,但减少LLC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。桔梗皂苷D能促进细胞缝隙连接通讯和细胞溶酶体功能,促进自噬和自噬降解,抑制细胞P-gp表达。桔梗皂苷D在实验剂量对小鼠LLC肺部实体瘤生长无影响,增加肺组织摄取阿霉素和阿霉素对肺实体瘤的治疗效果。桔梗皂苷D改善肺实体瘤细胞外基质沉积,减少肺黏液蛋白5AC(mucin 5AC)分泌和肺血管通透性。总之,桔梗皂苷D对阿霉素治疗小鼠肺癌有导引作用,其机制与促进细胞通讯和溶酶体功能、改善细胞外环境有关。This study is to observe whether platycodin D has the guiding role in treatment of mouse lung cancer with doxorubicin and explore its guiding mechanism. In vitro, platycodin D and doxorubicin(alone or in combination) were added into Lewis lung cancer(LLC) cells to detect the cell proliferation and doxorubicin uptake. Cell morphological changes were analyzed by cell holographic analysis system;cell gap junctional intercellular communication(GJIC) was tested by fluorescent yellow tracer;lyso-tracker red was used to examine lysosomal function;LC-3 B(Light chain 3 beta)and P62(heat shock 90-like protein)staining were used to test auto-phagy and autophagic degradation respectively;and P-glycoprotein(P-gp) expression was examined by Western blot. In vivo, lung solid tumor was formed in mouse LLC cells via intravenous injection. Platycodin D and doxorubicin(alone or in combination) were used to treat tumor-bearing mice for four weeks, and then the tumor size was examined, mouse survival time was recorded, doxorubicin uptake in lung tissues was tested, and lung tissues were stained for observation by HE(hematoxylin-eosin) and immunohistochemistry. The results showed that platycodin D at the experimental concentration had no effect on LLC cell proliferation but decreased LLC cell volume, promoted the cells to uptake doxorubicin and enhanced the inhibitory action of doxorubicin on cell proliferation. Platycodin D could promote GJIC and lysosomal function, increase autophagy and autophagic degradation and suppress P-gp expression. Platycodin D at the experimental dose in this study had no effect on LLC lung solid tumors in mice, increased doxorubicin uptake in lung tissues and enhanced the therapeutic efficacy of doxorubicin on lung solid tumors. Platycodin D could improve the extracellular matrix deposition in lung solid tumors, decreased the lung mucin 5 AC secretion and pulmonary vessel permeability. In summary, platycodin D had the guiding role in treating mouse lung cancer with doxorubicin, and its guiding mechanism ma

关 键 词：桔梗皂苷D 阿霉素 肺癌 导引机制 

分 类 号：R285.5[医药卫生—中药学]