Effects of Pachyman in Combination with Vinorelbine and Cisplatin on Tumor Growth and the Expression of EGFR and K-ras in Mice with Lung Cancer  

茯苓多糖联合长春瑞滨和顺铂对肺癌小鼠模型肿瘤生长及EGFR、K-ras基因表达的影响（英文）

作　　者：Ke WEI Jia-Hao ZHOU Yong-Chao CHEN Jia-Ming TIAN Meng-Jin SUN Xin-Wen DAI Bai-Hui LI Ling LI Fang-Liang ZHOU Yi NING Jue HU Qin XIANG Bo ZHANG Fang-Guo LU 魏科;周家豪;陈勇超;田佳铭;孙梦锦;戴鑫汶;李柏慧;李玲;周芳亮;宁毅;胡珏;向琴;张波;卢芳国(湖南中医药大学医学院;湖南补天药业有限公司)

机构地区：[1]School of Medicine,Hunan University of Chinese Medicine,Changsha,Hunan 410208,China [2]Hunan Busky Pharmaceutical Co.,Ltd,Changsha,Hunan 410005,China

出　　处：《Digital Chinese Medicine》2018年第4期310-315,共6页数字中医药（英文）

基　　金：support from the National Natural Science Foundation of China(No.81774126,No.81503445 and No.81703919);China Postdoctoral Science Foundation(No.2017M622587);Hunan Provincial Natural Science Foundation(No.2016JJ2095 and No.2017JJ3232);Hunan Provincial Traditional Chinese Medicine Key Research Project(No.201701);Hunan Education Department Scientific Research Project(16C1203 and 16C1216);Hunan Health Department Scientific Research Project(C2015-16,C2016049 and B2016093);Busky Pharmaceutical Collaborative Research Fund,Hunan Provincial Higher Educational Institutions Research Team "Traditional Chinese Medicine prevention and treatment research on infectious diseases" Funding program(No.15);Hunan Province Teaching and Science "Thirteenth Five-Year Plan" Project(No.XJK17BGD057)

摘　　要：Objective To examine the effects of pachyman in combination with vinorelbine and cisplatin on tumor growth and the expression of epidermal growth factor receptor(EGFR)and K-ras in a mouse model of lung cancer induced using the human lung cancer cell line A549,and to investigate the molecular mechanisms underlying the antitumor effects of pachyman.Methods We recorded the size of the tumor xenografts in mice after treatment with pachyman monotherapy or pachymanin combination with vinorelbine and cisplatin.We performed immunohistochemical analysis to determine the levels of expression and distribution of EGFR and K-ras in lung cancer tissues.Real-time fluorescence quantitative PCR was used to determine the relative mRNA expression levels of EGFR and K-ras in lung cancer tissues.Results Vinorelbine and cisplatin significantly decreased the rate of growth of A549 xenografts,and pachyman increased the efficacy of vinorelbine and cisplatin.EGFR and K-ras were widely expressed in A549 xenografts.Vinorelbine and cisplatin could significantly decrease the expression,distribution and mRNA expression levels of EGFR and K-ras in tumor tissues.Pachyman monotherapy significantly decreased the distribution and the mRNA expression levels of EGFR in lung cancer tissues.In addition,pachyman in combination with vinorelbine and cisplatin markedly decreased the distribution and expression levels of EGFR in lung cancer tissues.However,pachyman monotherapy or combination therapy did not significantly decrease the mRNA expression levels of K-ras.Conclusion Thus,pachyman in combination with vinorelbine can significantly inhibit the growth of A549 xenografts,and pachyman can regulate the expression of the EGFR gene to increase the efficacy of vinorelbine and cisplatin in lung cancer and decrease the side effects associated with chemotherapy.目的研究茯苓多糖联合长春瑞滨和顺铂对人肺癌细胞系A549成瘤小鼠的肿瘤生长及EGFR、K-ras基因表达的影响,初步探讨茯苓多糖作用于肿瘤的分子机制。方法常规记录茯苓多糖单用或联合长春瑞滨和顺铂治疗后成瘤小鼠肿瘤的生长大小。应用免疫组化技术研究EGFR、K-ras基因在肺癌组织中的表达和分布情况,并通过实时荧光定量PCR检测EGFR、K-ras基因在肺癌肿瘤组织中mRNA的相对表达量。结果长春瑞滨和顺铂能够显著降低A549细胞成瘤的生长速度,茯苓多糖具有辅助增强长春瑞滨和顺铂的治疗效果的作用。EGFR、K-ras广泛表达于A549细胞的成瘤组织中。长春瑞滨和顺铂能够显著降低EGFR、K-ras两个基因在肿瘤组织中的表达分布和mRNA的表达水平。单用茯苓多糖能够降低EGFR在肺癌组织中的分布及其mRNA的表达量,茯苓多糖联用长春瑞滨和顺铂,能够进一步降低EGFR在肺癌组织中的分布和表达量,但是茯苓多糖单用或联用均未表现出明显降低K-ras基因的mRNA表达量。结论茯苓多糖联合长春瑞滨和顺铂对A549细胞成瘤组织具有明显的抑制生长作用,并且茯苓多糖通过调节EGFR基因的表达,辅助增强长春瑞滨和顺铂对肺癌的治疗效果,改善化疗的副作用。

关 键 词：Pachyman VINORELBINE CISPLATIN Lung cancer EGFR K-RAS 

分 类 号：R734.2[医药卫生—肿瘤] R-332[医药卫生—临床医学]