淫羊藿苷通过IL-6/STAT3通路逆转肺癌A549/DDP细胞顺铂耐药的作用机制研究  

Study on the Mechanism of Icariin Reversing Cisplatin Resistance in Lung Cancer A549/DDP Cells Through IL-6/STAT3 Pathway

作　　者：宁丞君 王瑜 胡邵霖 NING Chengjun;WANG Yu;HU Shaolin(Xinyang Central Hospital,Xinyang,464000)

机构地区：[1]河南省信阳市中心医院,464000

出　　处：《实用癌症杂志》2023年第8期1233-1238,共6页The Practical Journal of Cancer

摘　　要：目的 探讨淫羊藿苷(ICA)对A549/DDP细胞顺铂耐药的逆转作用及对白细胞介素-6(IL-6)和信号传导子及转录激活子3(STAT3)信号通路的调节。方法 第4代对数生长期的A549/DDP细胞随机分为A549/DDP组和ICA组,MTT法检测不同浓度ICA对细胞增殖率的影响。采用不同浓度DDP及50、100μmol/L ICA处理A549/DDP细胞,MTT法检测ICA对A549/DDP细胞化疗敏感性的影响。采用4μg/mL DDP和50、100μmol/L ICA处理A549/DDP细胞,流式细胞仪检测细胞凋亡率,Transwell试验检测细胞侵袭能力,qRT-PCR检测细胞中肺耐药蛋白(LRP)和多药耐药蛋白(MRP) mRNA相对表达量,蛋白印迹法检测IL-6、STAT3、B细胞淋巴瘤-2(Bcl-2)和Bcl-2相关X蛋白(Bax)蛋白相对表达量。结果 细胞增殖率随ICA浓度的增加而降低(P<0.05)。与单独使用不同浓度DDP处理A549/DDP细胞比较,50和100μmol/L ICA处理提高细胞对DDP的敏感性,降低DDP对细胞的半数抑制浓度(IC50)(P<0.05)。50和100μmol/L ICA处理A549/DDP细胞,细胞侵袭能力减弱、LRP和MRP mRNA相对表达量以及IL-6、STAT3和Bcl-2蛋白相对表达量降低,细胞凋亡率和Bax蛋白相对表达量升高。结论 ICA可增强A549/DDP细胞对DDP的敏感性,逆转耐药性,其可能是通过抑制IL-6/STAT3信号通路发挥作用。Objective To investigate the reversal effect of icariin(ICA) on cisplatin resistance in A549/DDP cells and the regulation of interleuk-6(IL-6) and signal transductor and transcriptional activator 3(STAT3) signaling pathways.Methods The 4th generation of A549/DDP cells in logarithmic growth phase were randomly divided into A549/DDP group and ICA group.The effect of ICA concentration on cell proliferation was detected by MTT assay.A549/DDP cells were treated with different concentrations of DDP and 50 and 100 μmol/L ICA,and the effect of ICA on the chemotherapy sensitivity of A549/DDP cells was detected by MTT assay.A549/DDP cells were treated with 4 μg/mL DDP and 50 and 100 μmol/L ICA.The apoptosis rate of A549/DDP cells was detected by flow cytometry,and the invasion ability of A549/DDP cells was detected by transwell test.The mRNA relative expression levels of lung drug resistance protein(LRP) and multidrug resistance associated protein(MRP) were detected by qRT-PCR,and the relative expression levels of IL-6,STAT3,B-cell lymphoma-2(Bcl-2) and Bcl-2 associated X protein(Bax) were detected by western blotting.Results The cell proliferation rate was decreased with the increase of ICA concentration(P<0.05).Compared with A549/DDP cells treated with different concentrations of DDP alone,50 and 100 μmol/L ICA increased the sensitivity of cells to DDP,and decreased the half inhibitory concentration(IC50) of DDP(P<0.05).A549/DDP cells were treated with ICA at 50 and 100 μmol/L,and the invasion ability,mRNA relative expressions of LRP and MRP,and relative expressions of IL-6,STAT3 and Bcl-2 proteins were decreased,while the apoptosis rate and the relative expression of Bax protein were increased.Conclusion ICA can enhance the sensitivity of A549/DDP cells to DDP and reverse drug resistance,which may play a role by inhibiting IL-6/STAT3 signaling pathway.

关 键 词：A549/DDP细胞 耐药 IL-6/STAT3 淫羊藿苷 

分 类 号：R734.2[医药卫生—肿瘤]