南方医科大学学报2026，Vol.46Issue(3)：523-531,9.DOI:10.12122/j.issn.1673-4254.2026.03.06
生脉散通过调控乳酸/Wnt/β-catenin/LDHA通路改善非小细胞肺癌奥希替尼耐药的作用机制
Shengmai San improves osimertinib resistance of non-small cell lung cancer cells by regulating the lactate/Wnt/β-catenin/LDHA pathway
摘要
Abstract
Objective To explore the effect of Shengmai San(SMS)for improving osimertinib resistance in non-small cell lung cancer cells and the underlying mechanism.Methods Cultured A549 cells were treated with osimertinib alone or in combination with SMS-medicated rat serum,and the changes in cell viability and glucose and lactate levels were determined.The effect of SMS combined with osimertinib for improving osimertinib resistance of A549 cells was assessed in a mouse model bearing subcutaneous A549 cell xenograft.Western blotting,RT-qPCR,and immunofluorescence staining were used to analyze the effects of SMS and lactate on the Wnt/β-catenin/LDHA signaling pathway.Results SMS significantly increased osimertinib sensitivity of A549 cells in a concentration-dependent manner.Compared with osimertinib alone,the combined treatment with SMS and osimertinib significantly inhibited cell viability,colony formation ability,and tumor growth in nude mice.SMS concentration-dependently decreased glucose and lactate levels in A549 cells.The results of Western blotting showed that SM inhibited the protein expression of LDHA,total β-catenin,and cytoplasmic and nuclear β-catenin,while lactate obviously activated the expressions of total β-catenin protein,nuclear β-catenin,and LDHA in A549 cells.Immunofluorescence concentration-dependent staining showed that lactic acid activated nuclear accumulation of β-catenin protein,while SMS significantly inhibited the expression of nuclear β-catenin protein;RT-qPCR demonstrated that lactate significantly increased mRNA expressions of the Wnt/β-catenin downstream target genes(c-myc,CD44,Axin2,Oct3/4,survivin,and CCND1),while SMS inhibited their expressions.Conclusion SMS improves osimertinib resistance in non-small cell lung cancer cells by inhibiting lactate/Wnt/β-catenin/LDHA pathway-mediated glycolysis.关键词
生脉散/非小细胞肺癌/奥希替尼耐药/糖酵解/乳酸/机制/Wnt/β-catenin信号通路/乳酸脱氢酶AKey words
Shengmai San/non-small cell lung cancer/osimertinib resistance/glycolysis/lactate/mechanism Wnt/β-catenin pathway/lactate dehydrogenase A引用本文复制引用
梁芷晴,潘富珍,邓利强,麦哲芬,马云,施传坚,付卫明..生脉散通过调控乳酸/Wnt/β-catenin/LDHA通路改善非小细胞肺癌奥希替尼耐药的作用机制[J].南方医科大学学报,2026,46(3):523-531,9.基金项目
国家自然科学基金青年科学基金(C类)(82505309) （C类）
中国博士后科学基金面上项目(2024M760671) （2024M760671）
广东省医学科学基金青年项目(B2025082) （B2025082）
广州中医药大学校院联合科技创新基金-深圳医院(GZYFT2024G12),经方与现代中药融合创新全国重点实验室开放课题一般项目(LSLSKL20240118)Supported by National Natural Science Foundation of China(82505309). （GZYFT2024G12）
