“扶正祛积汤”联合埃克替尼通过细胞周期阻滞机制协同抑制肺腺癌A549细胞裸鼠移植瘤增殖的研究  

Effect of Fuzheng Quji Decoction Combined with Icotinib on Proliferation of Transplanted Lung Adenocarcinoma A549 Cells in Nude Mice Via Cell Cycle Arrest

作　　者：赵同伟[1,2] 卢丽琴 应栩华[3] 潘智敏 张建宾[1,2] 梁卫青[3] 李厥宝 罗利民[6] 毕爱红[6] 袁国荣[1,2] ZHAO Tongwei;LU Liqin;YING Xuhua;PAN Zhimin;ZHANG jianbin;LIANG Weiqing;LI Juebao;LUO Limin;BI Aihong;YUAN Guorong(Department of Oncology,Zhejiang Provincial People’s Hospital,Hangzhou 310014,Zhejiang,China;Department of Oncology,People’s Hospital of Hangzhou Medical College,Hangzhou 310014,Zhejiang,China;Zhejiang Academy of Traditional Chinese Medicine,Hangzhou 310007,Zhejiang,China;Geriatric Department of Zhejiang Province Hospital of TCM,Hangzhou 310006,Zhejiang,China;Department of Rehabilitation,Zhejiang Provincial People’s Hospital,Hangzhou 310014,Zhejiang,China;Department of Radiotherapy,Zhejiang Provincial People’s Hospital,Hangzhou 310014,Zhejiang,China)

机构地区：[1]浙江省人民医院肿瘤内科,浙江杭州310014 [2]杭州医学院附属人民医院肿瘤内科,浙江杭州310014 [3]浙江省中医药研究院,浙江杭州310007 [4]浙江省中医院干部科,浙江杭州310006 [5]浙江省人民医院康复科,浙江杭州310014 [6]浙江省人民医院放疗科,浙江杭州310014

出　　处：《中华中医药学刊》2019年第5期1196-1200,I0027-I0028,共6页Chinese Archives of Traditional Chinese Medicine

基　　金：浙江中医药科技计划项目(2013ZA015);浙江科技厅公益性技术应用研究项目(2015C37089);浙江省中医药科技计划项目(2018ZB014)

摘　　要：目的:从诱导细胞周期阻滞机制研究中药"扶正祛积汤"联合埃克替尼对肺腺癌细胞A549裸鼠移植瘤的协同抑瘤作用。方法:(1)将A549细胞裸鼠移植瘤随机分成模型组、埃克替尼组、中药"扶正祛积汤"组和中药"扶正祛积汤"联合埃克替尼联合组(联合组),每组5只,按分组给药,21 d后处死裸鼠,计算各组抑瘤率和联合组增效率;(2)采用流式细胞仪检测各组移植瘤细胞周期分布情况;(3)采用免疫组化法和Western Blot法分别检测CDK4、Rb和Cyclin D1的表达水平。结果:(1)埃克替尼组、中药"扶正祛积汤"组和联合组的抑瘤率分别为14.74%、12.76%和31.25%,联合组增效率为111.11%,说明中药"扶正祛积汤"可以增效埃克替尼的抑瘤作用;(2)联合组G0/G1期细胞比例(54.51±0.35)%均明显高于埃克替尼组(49.39±0.27)%、"扶正祛积汤"组(47.59±1.05)%和模型组(45.88±0.24)%(P<0.05),细胞周期G1/S阻滞最更明显;(3)联合组瘤组织Cyclin D1和CDK4表达水平均低于埃克替尼组、中药"扶正祛积汤"组和模型组(均P<0.05),Rb表达则均高于上述3组(均P<0.05)。结论:中药"扶正祛积汤"可以增效埃克替尼对肺癌细胞A549裸鼠移植瘤的抑制增殖作用,其协同抑瘤机制可能和引起Cyclin D1、CDK4表达进一步下降和Rb表达进一步上升导致细胞周期G0/G1阻滞加重有关。Objective: To study the synergistic inhibitory effect of Fuzheng Quji Decoction combined with Icotinib on transplanted lung adenocarcinoma cell line A549 in nude mice via cell cycle arrest.Methods:(1)A549 cells were injected subcutaneously into the axillary of nude mice to form transplanted tumors. The mice were randomly divided into model group, Icotinib group, Fuzheng Quji Decoction group and Fuzheng Quji Decoction combined with Icotinib group(combined group). Five nude mice in each group were sacrificed after 21 days of administration.(2)Cell cycle distribution was detected by flow cytometry, and the expression of CDK4, Rb and Cyclin D1 were detected by immunohistochemistry and Western blot respectively.Results:(1)The tumor inhibition rates of Icotinib group, Fuzheng Quji Decoction group and combined group were 14.74%, 12.76% and 31.25% respectively, and the efficiency rate of the combined group was 111.11%.(2)The proportion of G0/G1 phase cells in the combined group[(54.51±0.35)%] was significantly higher than that in the Icotinib group[(49.39±0.27)%]. Fuzheng Quji Decoction group’s proportion of G0/G1 phase cells was(47.59±1.05)% and the model group’s was(45.88±0.24)%(P<0.05). The cell cycle G1/S block of the combined group was the most obvious.(3)The expression of Cyclin D1 and CDK4 in tumor tissues of the combined group was lower than that of Icotinib group, Fuzheng Quji Decoction group and model group(P<0.05), while the expression of Rb was higher than that of Icotinib group, Fuzheng Quji Decoction group and model group(P<0.05).Conclusion: Fuzheng Quji Decoction can enhance the inhibitory effect of Icotinib on the inhibition of proliferation of transplanted tumors of lung cancer cell A549 in nude mice. The synergistic tumor suppressor mechanism may be related to the aggravation of G0/G1 phase arrest which is related to the further decrease of Cyclin D1 and CDK4 expression and the further increase of Rb expression in comparision with Icotinib.

关 键 词：扶正祛积汤 埃克替尼 肺肿瘤 细胞周期阻滞 

分 类 号：R285.5[医药卫生—中药学]