天佛参口服液对A549细胞体内外增殖的影响及机制研究  

Effect and mechanism of Tianfoshen Oral Liquidon proliferation of A549cells in vitroand in vivo

作　　者：张丹丹 翟云良 季芳 张亚云 夏扬 李全 王恒斌 ZHANG Dan-dan;ZHAI Yun-liang;JI Fang;ZHANG Ya-yun;XIA Yang;LI Quan;WANG Heng-bin(Lei Yun Shang Pharmaceutical Group Co.,Ltd.,Suzhou 215009,China)

机构地区：[1]雷允上药业集团有限公司,江苏苏州215009

出　　处：《中草药》2021年第21期6568-6575,共8页Chinese Traditional and Herbal Drugs

摘　　要：目的探究天佛参口服液对人非小细胞肺癌A549细胞与裸鼠移植瘤增殖的作用以及相关作用机制。方法采用Cell Titer-Glo发光法检测天佛参口服液对9种不同基因突变表型的肺癌细胞系增殖的抑制作用;采用流式细胞术检测天佛参口服液对A549细胞周期及凋亡的影响;采用Western blotting法考察天佛参口服液对A549细胞增殖相关蛋白表达的影响。裸鼠sc A549细胞建立裸鼠移植瘤模型,考察天佛参口服液对小鼠皮下移植瘤生长的影响。结果天佛参口服液抑制A549细胞增殖,呈剂量相关性;天佛参口服液阻滞A549细胞周期于G_(0)/G_(1)期和G_(2)/M期(P<0.05、0.01),并且1%天佛参口服液可以显著诱导A549细胞凋亡(P<0.01);天佛参口服液显著抑制表皮生长因子受体(epidermal growth factor receptor,EGFR)、Raf、丝裂原细胞外信号调节激酶(mitogen extracellular signal-regulated kinase,MEK)以及细胞外调节蛋白激酶(extracellular regulated protein kinase,ERK)蛋白的磷酸化水平(P<0.05、0.01),呈剂量相关性。体内实验结果显示,2.25 mL/kg天佛参口服液对裸鼠移植瘤模型的肿瘤体内生长具有显著抑制作用(P<0.05)。结论天佛参口服液对A549细胞的体内外生长具有显著抑制作用,其作用机制可能与抑制EGFR活性和下调Ras/Raf/MEK/ERK信号通路表达有关。Objective To investigate the effect and related mechanism of Tianfoshen Oral Liquid(天佛参口服液)on cell proliferation in A549 cells and lung cancer mice transplantable tumor in model animals.Methods Cell Titer-Glo assay was used to detect the inhibitory effect of Tianfoshen Oral Liquid onproliferation of ninedifferent gene mutation phenotypes of lung cancer cell lines;Flow cytometry was applied to determine the effect of Tianfoshen Oral Liquid on cell cycle and apoptosis of A549 cells;Western blotting was used to explore the effect of Tianfoshen Oral Liquid on expression of proliferation-related proteins in A549 cells.Nude mice were sc A549 cells to establish nude micexenograft tumor model,the effect of Tianfoshen Oral Liquid on growth of subcutaneous xenograft tumors in micewasinvestigated.Results Tianfoshen Oral Liquid inhibitedthe proliferation of A549 cells,withdose-dependent;Tianfoshen Oral Liquid blocked the A549 cell cycle in G_(0)/G_(1)and G_(2)/M phases(P<0.05,0.01),and 1%Tianfoshen Oral Liquid significantly inducedapoptosis of A549 cells(P<0.01);Tianfoshen Oral Liquid significantly inhibitedepidermal growth factor receptor(EGFR),Raf,mitogen extracellular signal-regulated kinase(MEK)and extracellular regulated protein kinase(ERK)protein phosphorylation levels(P<0.05,0.01),showing a dose-dependent.The results of in vivoexperiments showed that 2.25 mL/kg Tianfoshen Oral Liquid had a significant inhibitory effect on tumor growth in nude mice transplanted tumor models(P<0.05).Conclusion Tianfoshen Oral Liquid has a significant inhibitory effect on growth of A549 cells in vivoand in vitro,and its mechanism may be related to the inhibition of EGFR activity and down-regulation of Ras/Raf/MEK/ERK signal pathway expression.

关 键 词：天佛参口服液 肺癌 A549细胞 增殖 裸鼠移植瘤模型 抗肿瘤 

分 类 号：R285.5[医药卫生—中药学]