“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

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。

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

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)