AKR1C3通过PD1/PD-L1信号通路对乳腺癌细胞恶性生物学行为的干预作用OA
Intervention of AKR1C3 on Malignant Biological Behavior of Breast Cancer Cells through PD1/PD-L1 Signaling Pathway
目的 探索酮还原酶家族 1 成员C3(aldo-keto reductase family 1 member C3,AKR1C3)对乳腺癌恶性细胞生物学行为的干预作用及对程序性细胞死亡蛋白/程序性死亡-配体 1(programmed cell death protein1/programmed death-ligand1,PD-1/PD-L)通路的影响.方法 把MCF-7 人乳腺癌细胞中NC组和AKR1C3 组分别转染空质粒和AKR1C3 质粒,采用MTT法检测转染后 24 h、48 h、72 h细胞活力;采用流式细胞技术测定各组细胞的存活率以及早期、晚期凋亡比例;通过Transwell实验对各组细胞的迁移和侵袭能力进行检测;通过Western blot检测各组细胞PD-1、PD-L1、蛋白激酶B(protein kinase b,AKT)蛋白表达水平.使用C57BL/6 小鼠构建荷瘤模型,将采用人乳腺癌MCF-7 细胞转染NC质粒和AKR1C3 质粒进行细胞荷瘤,每3 d测量瘤体积,持续 21 d,绘制两组小鼠肿瘤生长曲线,并于实验终点测量肿瘤质量.结果 相较于NC组,AKR1C3 组细胞活力降低(P<0.05),并且具有时间依赖效应(P<0.05),迁移和侵袭能力降低(P<0.05),早期凋亡和晚期凋亡比例升高(P<0.05),PD-1、PD-L1、AKT蛋白表达水平降低(P<0.05).动物实验表明,AKR1C3 组小鼠肿瘤体积降低,肿瘤质量下降(P<0.05).结论 AKR1C3 可以抑制人乳腺癌细胞恶性生物学行为,抑制PD-1/PD-L1 信号通路蛋白表达.
Objective To investigate the effect of aldo-keto reductase family 1 member C3(AKR1C3)on malignant biological behavior of breast cancer cells and its influence on the programmed cell death protein 1/programmed death-ligand 1(PD-1/PD-L1)pathway.Methods MCF-7 human breast cancer cells with NC and AKR1C3 groups transfected with NC plasmid and AKR1C3 plasmid respectively.Cell viability at 24 h/48 h/72 h post-transfection was assessed by MTT assay;flow cytometry measured cell survival rate and early/late apoptosis ratios;Transwell evaluated migration and invasion capabilities;western blot detected PD-1,PD-L1,protein kinase B(AKT)protein expression.For in vivo experiments,the C57BL/6 mice were used to establish tumor-bearing models.Human breast cancer MCF-7 cells transfected with NC plasmid and AKR1C3 plasmid were used for cell tumor-bearing.The tumor volume was measured every 3 days for 21 days,draw the tumor growth curves of the two groups of mice and measure the tumor mass at the end of the experiment.Results Compared to NC groups,the AKR1C3 group showed significantly reduced cell viability(time-dependent)(P<0.05),suppressed m igration/invasion(P<0.05),increased early/late apoptosis ratios(P<0.05),and downregulated PD-1/PD-L1/AKT protein expression(P<0.05).In vivo,AKR1C3 group exhibited reduced tumor volume and weight(P<0.05).Conclusion AKR1C3 inhibits malignant biological behaviors in breast cancer cells and suppresses PD-1/PD-L1 signaling pathway protein expression.
宋晶晶;熊伟;姚淑辉;刘爽;张静
河北省唐山市人民医院放化七科,河北 唐山 063000河北省唐山市人民医院放化七科,河北 唐山 063000河北省唐山市人民医院放化七科,河北 唐山 063000河北省唐山市人民医院放化七科,河北 唐山 063000河北省唐山市人民医院放化七科,河北 唐山 063000
医药卫生
AKR1C3人乳腺癌凋亡迁移PD-1/PD-L1通路侵袭AKTPPR5
AKR1C3Human breast cancerApoptosisMigrationPD-1/PD-L1 pathwayInvasionAKTPPR5
《昆明医科大学学报》 2026 (1)
31-38,8
唐山市人力项目(A202110017)
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