中国肿瘤生物治疗杂志2024，Vol.31Issue(4)：333-341,9.DOI:10.3872/j.issn.1007-385x.2024.04.003
基于EGFR/AKT和JAK2/STAT3通路研究α-常春藤皂苷单独或与顺铂联用对非小细胞肺癌细胞增殖与凋亡的影响
Effects of α-hederin alone or in combination with cisplatin on the proliferation and apoptosis of non-small cell lung cancer cells based on EGFR/AKT and JAK2/STAT3 pathways
摘要
Abstract
Objective:To explore the targets and potential mechanism of α-hederin(α-Hed)inducing cell apoptosis on non-small cell lung cancer(NSCLC),and to clarify the effects of α-Hed in combination with cisplatin(DDP)on the expression of target proteins.Methods:The viability of NSCLC cells(A549,H1299 and PC-9 cells)treated with different concentrations of α-Hed was detected by CCK-8 method.The apoptosis rate was determined by flow cytometry with Annexin Ⅴ-FITC/PI staining.The expressions of cleaved caspase-3(C-caspase-3)and Bcl-2 proteins were detected by Western blot.The potential targets of α-Hed were screened by network pharmacology,and their binding effect was analyzed by molecular docking method.Besides,Western blot was applied to detect target protein expression.The suppressive effect of α-Hed in combination with DDP on NSCLC cells was detected by CCK-8 assay,colony formation assay and Western blot assay.Results:After 24 h and 48 h administration,α-Hed at 10,15 and 20 μmol/L significantly inhibited the proliferation viability of NSCLC cells(all P<0.01).Compared with the control group,the apoptosis rate significantly increased after 20 μmol/L α-Hed treatment(P<0.01).C-caspase-3 expression in NSCLC cells was upregulated(P<0.05)and Bcl-2 expression was downregulated after α-Hed administration.The targets of AKT1,STAT3,EGFR and JAK2 with the binding affinity less than-5 kcal/mol were screened out via network pharmacology and molecular docking.Western blot showed that the expressions of EGFR,p-AKT/AKT,p-STAT3/STAT3 and JAK2 proteins in A549 and H1299 cells were significantly downregulated after α-Hed treatment(all P<0.05).Furthermore,α-Hed in combination with DDP more significantly inhibited the proliferation of NSCLC cells(P<0.01)and downregulated the expression of EGFR,p-AKT/AKT,p-STAT3/STAT3 and JAK2 proteins(P<0.05 or P<0.01).Conclusion:α-Hed induces the apoptosis of NSCLC by down-regulating EGFR and JAK2 expressions,and inhibiting the phosphorylation of STAT3 and AKT.Especially,the inhibitory effect is enhanced when α-Hed is used in combination with DDP,and the EGFR/AKT and JAK2/STAT3 pathways are further inhibited.关键词
α-常春藤皂苷/非小细胞肺癌/增殖/凋亡/AKT1/STAT3/EGFR/JAK2Key words
α-hederin(α-Hed)/non-small cell lung cancer(NSCLC)/proliferation/apoptosis/AKT1/STAT3/EGFR/JAK2分类
医药卫生引用本文复制引用
朱志明,王苏美,唐青,王晰,万信良,莫瀚丹,贾璐瑜,俞晓燕,周绮纯..基于EGFR/AKT和JAK2/STAT3通路研究α-常春藤皂苷单独或与顺铂联用对非小细胞肺癌细胞增殖与凋亡的影响[J].中国肿瘤生物治疗杂志,2024,31(4):333-341,9.基金项目
广东省中医院拔尖人才科研专项(No.BJ2022KY13) （No.BJ2022KY13）
广东省中医药局面上项目(No.20222085,No.20231094) （No.20222085,No.20231094）
