CAJ | 학술논문

目的：探究线粒体雌激素受体β（ERβ）抑制凋亡刺激诱导非小细胞肺癌细胞死亡的分子机制。方法免疫荧光及western blotting分析细胞内源ERβ的线粒体定位；检测顺铂与十字孢碱（staurosporine，STS）处理过表达或沉默线粒体ERβ后细胞凋亡的变化；免疫共沉淀和western blotting分析线粒体ERβ与促凋亡蛋白Bad的相互作用。结果 ERβ存在于A549及201T细胞的线粒体中；过表达或沉默ERβ可以显著减少或增加顺铂与STS诱导的Bax激活及细胞凋亡；线粒体ERβ与促凋亡蛋白Bad相互作用可能阻抑Bax的活化及线粒体转位。结论线粒体雌激素受体β可以通过与Bad相互作用抑制顺铂或STS诱导非小细胞肺癌细胞的凋亡，提示线粒体ERβ可能是治疗非小细胞肺癌的一个新靶点。
목적：탐구선립체자격소수체β（ERβ）억제조망자격유도비소세포폐암세포사망적분자궤제。방법면역형광급western blotting분석세포내원ERβ적선립체정위；검측순박여십자포감（staurosporine，STS）처리과표체혹침묵선립체ERβ후세포조망적변화；면역공침정화western blotting분석선립체ERβ여촉조망단백Bad적상호작용。결과 ERβ존재우A549급201T세포적선립체중；과표체혹침묵ERβ가이현저감소혹증가순박여STS유도적Bax격활급세포조망；선립체ERβ여촉조망단백Bad상호작용가능조억Bax적활화급선립체전위。결론선립체자격소수체β가이통과여Bad상호작용억제순박혹STS유도비소세포폐암세포적조망，제시선립체ERβ가능시치료비소세포폐암적일개신파점。
Objective To explore the molecular mechanisms by which mitochondrial estrogen receptorβ(ERβ) suppresses non-small cell lung cancer cell apoptosis induced by apoptotic stimulations. Methods The mitochondrial localization of ERβin non-small cell lung cancer cell lines A549 and 201T was determined using immunofluorescence and Western blotting. The changes of apoptosis of the cells with mitochondrial ERβ overexpression or knockdown in response to cisplatin and STS treatments were assessed, and mitochondrial ERβ interaction with the pro- apoptotic protein Bad was detected using co-immunoprecipitation and Western blotting. Results ERβ was localized in the mitochondria in A549 and 201T cells. ERβoverexpression significantly reduced while ERβknockdown increased Bax activation and cell apoptosis induced by cisplatin and STS. Mitochondrial ERβinteraction with pro-apoptotic protein Bad may suppress Bax activation and its translocation to the mitochondria. Conclusion Mitochondrial ERβ can suppress apoptosis of non-small cell lung cancer cells induced by cisplatin or STS through interaction with Bad, suggesting the value of mitochondrial ERβ as a new therapeutic target for treatment of non-small cell lung cancer.