世界中医药
文章摘要
引用本文:黄璐璐1,杜倩倩1,闫辰1,刘春霞1,李芋润2,高林3,李燕1,赵青4.睿臻对肺癌的抑制作用及其机制[J].世界中医药,2018,(06):.  
睿臻对肺癌的抑制作用及其机制
Anti-tumor Activity and Molecular Mechanisms of Rui Zhen in Lung Cancer
投稿时间:2018-03-28  
DOI:10.3969/j.issn.1673-7202.2018.06.049
中文关键词:  睿臻  肺癌  增殖  凋亡  侵袭  增效减毒  Raf/MEK/ERK  FAK/p38
English Keywords:Rui Zhen  Lung cancer  Proliferation  Apoptosis  Invading  Efficacy enhancing and toxicity reducing  Raf/MEK/ERK  FAK/p38
基金项目:中国医学科学院医学与健康科技创新工程-重大协同创新项目(2016-I2M-1-008)
作者单位
黄璐璐1,杜倩倩1,闫辰1,刘春霞1,李芋润2,高林3,李燕1,赵青4 1 中国医学科学院北京协和医学院药物研究所北京100050 2 青海省第四人民医院西宁810000 3 青海睿元药物研究所有限责任公司西宁810003 4 中国医学科学院、北京协和医学院基础医学研究所北京100730 
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中文摘要:
      目的:初步探讨由山楂、沙棘和枸杞三味中药为主,并添加虫草素、虫草多糖、β-葡聚糖和番茄红素等制备而成的天然药物组方睿臻的体内外抗肺癌活性及其机制。方法:采用MTT法检测睿臻体外抗肿瘤活性,小鼠Lewis移植瘤模型观察单独使用睿臻及联合紫素的抗肺癌活性及对荷瘤小鼠生存时间的影响。FCM实验检测其对肿瘤细胞凋亡的影响,重组基质膜侵袭实验观察对肿瘤细胞侵袭能力的影响,Western blot方法初步探讨该化合物的作用机制。结果:睿臻对肺癌细胞具有较好的增殖抑制活性,其作用于A549细胞株、NCI-H460细胞株和NCI-H1975细胞株120 h后的IC50值分别为98.42 μg/mL、60.02 μg/mL和60.41 μg/mL;睿臻也可显著抑制小鼠Lewis肺癌的生长,9.0 g/kg睿臻对小鼠Lewis肺癌的生长抑制率达70.0%,且可在增强紫素的抗肿瘤活性的同时升高胸腺指数及外周血中红细胞数量和血红蛋白水平。睿臻可延长Lewis肺癌小鼠的生存时间。睿臻可诱导肺癌细胞A549和NCI-H460发生凋亡。在96.0 μg/mL和192.0 μg/mL剂量下,可显著抑制肺癌细胞穿过重组基底膜的数量。Western blot结果显示睿臻可抑制Raf/MEK/ERK、FAK/p38等信号通路。结论:睿臻在体内外均具有一定的抗肺癌活性,其作用机制可能与阻断Raf/MEK/ERK信号转导通路有关,有望开发成为肺癌治疗的天然药物制剂。
English Summary:
      To investigate the anti-tumor effect and mechanisms of Rui Zhen which contains hawthorn, hippophae, medlar, cordycepin, cordyceps polysaccharide, β-glucan and lycopeneon.Methods:MTT assay was used to analyze anti-proliferation activity of Rui Zhen in vitro.Anti-tumor activity and the effect of survival time were observed by mouse Lewis xenograft model in vivo.The effect of Rui Zhen on apoptosis was measured by FCM analysis.Western blot was performed to investigate the expression level of proteins in tumor tissues treated with Rui Zhen.Results:Rui Zhen has a good proliferation inhibitory activity on lung cancer cells.The IC50 values of A549 cell line, NCI-H460 cell line and NCI-H1975 cell line after 120 h were 98.42 μg/mL, 60.02 μg/mL and 60.41 μg/mL respectively.Rui Zhen can also significantly inhibit the growth of Lewis lung cancer in mice, and the growth inhibition rate of 9.0 g/kg ruthenium on Lewis lung cancer in mice was 70.0%, and it can enhance the purple pigment.The anti-tumor activity increased both the thymus index and the number of red blood cells and hemoglobin in the peripheral blood.Rui Zhen can prolong the survival time of Lewis lung cancer mice.Rui Zhen can induce apoptosis of lung cancer cells A549 and NCI-H460.At 96.0 μg/mL and 192.0 μg/mL, the number of lung cancer cells passing through the reconstituted basement membrane was significantly inhibited.Western blot results showed that ruthenium can inhibit Raf/MEK/ERK, FAK/p38 and other signaling pathways.Conclusion:Rui Zhen has certain anti-lung cancer activity in vitro and in vivo, and its mechanism may be related to blocking Raf/MEK/ERK signal transduction pathway.It is expected to develop into a natural pharmaceutical preparation for lung cancer treatment.
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