肿瘤防治研究2023，Vol.50Issue(12)：1185-1190,6.DOI:10.3971/j.issn.1000-8578.2023.23.0310
非小细胞肺癌EGFR-TKI靶向治疗与细胞焦亡的关系
Relationship of EGFR-TKI Targeted Therapy and Pyroptosis in Non-small Cell Lung Cancer
陈家琛 1吴听雨 1夏伟梁1
作者信息
- 1. 200030 上海,上海交通大学生物医学工程学院
- 折叠
摘要
Abstract
Objective To explore the relationship between pyroptosis and treatment in non-small cell lung cancer patients treated with tyrosine kinase inhibitors targeted therapy.Methods Stable transfection strains with common EGFR mutations found in clinical practice were constructed through lentiviral transfection.LDH and Western blot experiments were conducted to determine the degree and mechanism of pyroptosis after osimertinib treatment.Animal experiments verified the effect of pyroptosis on treatment efficacy.ELISA was used to explore the potential connection between pyroptosis and tumor immunotherapy.Results After osimertinib treatment on stable lines,the EGFR-L858R mutation had obvious pyroptosis at the morphology and protein levels.Western blot experiment confirmed that pyroptosis was mediated by GSDME(P＜0.0001).Experiments through the overexpression of GSDME and corresponding animal studies discovered that the degree of pyroptosis affected the treatment outcome.Blood analysis revealed that the level of IL-1β secreted by EGFR-L858R and EGFR-L858R-GSDME-OE mice after treatment was higher than that of the control group(P＜0.0001),and it may regulate tumor immunity to a certain extent.Conclusion Osimertinib can induce pyroptosis in EGFR-L858R mutant strains mediated by GSDME,and the level of pyroptosis in cell lines is positively correlated with therapeutic effect to a certain extent.关键词
非小细胞肺癌/细胞焦亡/酪氨酸激酶抑制剂/奥希替尼Key words
Non-small cell lung cancer/Pyroptosis/Tyrosine kinase inhibitors/Osimertinib分类
医药卫生引用本文复制引用
陈家琛,吴听雨,夏伟梁..非小细胞肺癌EGFR-TKI靶向治疗与细胞焦亡的关系[J].肿瘤防治研究,2023,50(12):1185-1190,6.
