中药活性化合物高良姜素与吉非替尼抗非小细胞肺癌的协同增效作用及机制研究  

Study on the Synergistic Effect and Mechanism of Traditional Chinese Medicine Active Compound Galangin and Gefitinib on Non-Small Cell Lung Cancer

作　　者：沈存思[1] 杨福州 项莹颖 陈古月 纪建建 张正光[3] SHEN Cun-si;YANG Fu-zhou;XIANG Ying-ying;CHEN Gu-yue;JI Jian-jian;ZHANG Zheng-guang(Jiangsu Key Laboratory of Pediatric Respiratory Disease,Institute of Pediatrics,Nanjing University of Chinese Medicine,Nanjing,210023,China;School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing,210023,China;School of Medicine&Holistic Integrative Medicine,Nanjing University of Chinese Medicine,Nanjing,210023,China)

机构地区：[1]南京中医药大学中医儿科学研究所,江苏省儿童呼吸疾病(中医药)重点实验室,江苏南京210023 [2]南京中医药大学药学院,江苏南京210023 [3]南京中医药大学医学院·整合医学学院,江苏南京210023

出　　处：《南京中医药大学学报》2021年第1期72-76,共5页Journal of Nanjing University of Traditional Chinese Medicine

基　　金：国家自然科学基金(82004118,81904029);南京中医药大学自然科学基金青年项目(NZY82004118,NZY81904029);江苏省卫生健康委科研项目(Z2020015);江苏省高等学校自然科学研究面上项目(19KJB360010)。

摘　　要：目的探讨中药活性化合物高良姜素(Galangin)与肺癌靶向药物吉非替尼(Gefitinib)抗肺癌的协同增效作用及可能的分子机制。方法采用CCK-8及流式细胞术分别检测两药单用及联用时对A549细胞的增殖抑制作用及促凋亡作用;Western blot检测两者单用及联用时对各组凋亡相关蛋白及信号蛋白表达的影响。结果适宜浓度的Galangin与Gefitinib联用可更有效地抑制细胞增殖,促进细胞凋亡,协同作用显著;利用CompuSyn软件测得联合指数(Combination index,CI)<1;Western blot结果显示,与单用Gefitinib相比,两药联用可进一步降低p-EGFR、p-STAT3、Bcl-2的蛋白水平,提高Cleaved Caspase-3、Cleaved PARP、Bax的蛋白水平。结论在体外水平,Galangin与Gefitinib联用治疗非小细胞肺癌具有协同增效作用,对EGFR/STAT3信号通路相关蛋白的抑制作用可能是其机制之一,两者联用协同抗癌的作用值得关注。OBJECTIVE To explore the synergistic effect and possible molecular mechanism of TCM active compound Galangin and targeting drug Gefitinib on lung cancer.METHODS The growth inhibition and apoptosis-promoting effect of Gefitinib and Galangin on A549 cells were detected by CCK-8 and flow cytometry,respectively.Western blot was used to detect the protein expression levels of apoptosis-related proteins and signal proteins in each groups.RESULTS The combination for appropriate concentration of Galangin and Gefitinib more effectively inhibited the proliferation and promoted apoptosis of A549 cells,showing a good synergistic effect.The combination index(CI)measured by CompuSyn software less than 1.The results of Western blot showed that compared with Gefitinib alone,the combination of the two drugs further reduced the protein levels of p-EGFR,p-STAT3 and Bcl-2,and increased the protein levels of Cleaved Caspase-3,Cleaved PARP and Bax.CONCLUSION In vitro,the combination of Galangin and Gefitinib have synergistic effects in the treatment of non-small cell lung cancer,and the inhibition of the proteins expression related to EGFR/STAT3 signal pathway may be one of the mechanisms,suggesting that the synergistic anticancer mode of the combination for the two drugs should be concerned.

关 键 词：高良姜素 吉非替尼 非小细胞肺癌 联合指数 协同作用 

分 类 号：R734.2[医药卫生—肿瘤] R285.5[医药卫生—临床医学]