黄精-苍术药对通过Apex1/STAT3轴调控肺癌进展机制
Mechanism of Polygonati Rhizoma-Atractylodes Lancea regulating the progression of lung cancer through Apex1/STAT3 axis
秦晨歌 1岳利多 2李明 3范理宏4
作者信息
- 1. 南通大学医学院,南通 226007
- 2. 同济大学医学院能量代谢与健康研究所,上海 200000
- 3. 同济大学附属第十人民医院中西医整合医学科,上海 200000
- 4. 南通大学医学院,南通 226007;同济大学医学院能量代谢与健康研究所,上海 200000
- 折叠
摘要
目的:探讨黄精-苍术药对对非小细胞肺癌发展的影响及分子机制.方法:使用黄精-苍术药对干预人非小细胞肺癌NCI-H1299和PC9细胞,CCK-8实验评估细胞的活力,Edu荧光染色检测细胞增殖;使用C57BU6小鼠(KrasG12D/+;p53fl/fl)构建原发性肺癌小鼠模型,HE染色、免疫组化检测小鼠肺癌进展;通过qPCR和Western Blot检测Apex1 mRNA和蛋白的变化,通过流式细胞术和Western Blot检测细胞周期和细胞周期相关蛋白STAT3、CDK1、p21、p27表达.结果:黄精-苍术药对处理48 h后,人非小细胞肺癌NCI-H1299和PC9细胞增殖明显减弱.原发性肺癌小鼠模型构建成功;与对照组比较,黄精+苍术组小鼠原发性肺癌的进展显著受抑制.在体外细胞实验中,黄精-苍术药对呈浓度依赖性抑制Apex1和p-STAT3表达(P＜0.01,P＜0.05),同时下调CDK1蛋白表达(P＜0.01),增加p21和p27蛋白表达(P＜0.01),使NCI-H1299和PC9的细胞周期阻滞;该结果在动物实验中也得到验证.结论:黄精-苍术药对抑制非小细胞肺癌细胞的增殖,减缓了小鼠原发性肺癌的进展,通过抑制Apex1/STAT3信号通路,使肺癌细胞的细胞周期阻滞.
Abstract
Objective:To investigate the effects of Polygonati Rhizoma-Atractylodes Lancea on the development of non-small cell lung cancer(NSCLC)and its molecular mechanism.Methods:Human non-small cell lung cancer NCI-H1299 and PC9 cells were treated with Polygonati Rhizoma-Atractylodes Lancea.CCK-8 assay was used to evaluate the cell viability and Edu fluorescence staining was used to detect cell proliferation.C57BL/6 mice(KrasG12D/+;p53fl/fl)were used to establish a mouse model of primary lung cancer,and HE staining and immunohistochemistry were used to detect the progression of lung cancer.qPCR and Western Blot were used to analyze the expression level of Apex1 mRNA and protein,Western Blot and flow cytometry were used to analyze the expression level of STAT3,CDK1,p21,p27 and cell cycle.Results:After treated with Polygonati Rhizoma-Atractylodes Lancea for 48 hours,the proliferation of human non-small cell lung cancer NCI-H1299 and PC9 cells significantly decreased.The mouse model of primary lung cancer was successfully established,and compared with the control group,the progress of primary lung cancer in the treatment group was significantly inhibited.In the cell experiment in vitro,Polygonati Rhizoma-Atractylodes Lancea inhibited the expression of Apex1 and p-STAT3(P＜0.01,P＜0.05)in a concentration-dependent manner,down-regulated the expression of CDK1 protein(P＜0.01),increased the expression of p21 and p27 protein(P＜0.01),and blocked the cell cycle of NCI-H1299 and PC9 in a concentration-dependent manner,which was also verified in animal experiments.Conclusion:Polygonati Rhizoma-Atractylodes Lancea can inhibit the proliferation of NSCLC cells,slow down the progression of primary lung cancer in mice,and block the cell cycle of lung cancer cells by inhibiting Apex1/STAT3 signal pathway.
关键词
黄精/苍术/药对/非小细胞肺癌/Apex1/细胞周期Key words
Polygonati Rhizoma/Atractylodes Lancea/Herb pairs/Non-small cell lung cancer(NSCLC)/Apex1/Cell cycle引用本文复制引用
基金项目
国家自然科学基金项目(81473469)
一带一路国际合作项目(20400750600)
中西医结合创新旗舰医院建设项目(ZY2021-2023-0205-05)
中西医结合创新旗舰医院建设项目(ZXXT-202203)
出版年
2024
NETL
NSTL
万方数据