中国临床药学杂志2025，Vol.34Issue(1)：1-9,9.DOI:10.19577/j.1007-4406.2025.01.001
Serpinc1基因通过调控PI3K/AKT信号通路增强白蛋白结合型紫杉醇联合程序性死亡受体-1抗体的抗肺癌效果
Serpinc1 gene affects the anti-lung cancer efficacy of nab-PTX combined with anti-PD-1 antibody by regulating the PI3K/AKT signaling pathway
摘要
Abstract
AIM To investigate the efficacy and mechanisms of nab-PTX combined with anti-PD-1 antibody in treating lung cancer through the regulation of the PI3K/AKT signaling pathway.METHODS The mouse Lewis cells stably transfected with the Serpinc1 gene knockdown were used to construct a mouse model of subcutaneous transplanted tumor of lung cancer.The mice were randomly divided into different groups:the NC group,NC+nab-PTX group,NC+anti-PD-1 antibody group,NC+combined treatment group,shRNA group,shRNA+nab-PTX group,shRNA+anti-PD-1 antibody group,shRNA+combined treatment group,shRNA+740 Y-P group,shRNA+nab-PTX+740 Y-P group,shRNA+anti-PD-1 antibody+740 Y-P group,and shRNA+combined treatment+740 Y-P group.The anti-lung cancer effects of the Serpinc1 gene and its effects on the anti-lung cancer efficacy of nab-PTX combined with anti-PD-1 antibody in vivo were investigated by measuring tumor volume,tumor weight,survival time,hematoxylin and eosin(HE)staining in tumor tissues and lung tissues.The expression of Serpinc1 protein,and the phosphorylation levels of PI3K,AKT and NF-κB in tumor tissues were investigated by Western Blot,and the expression levels of Ki67 and TLR4 in tumor tissues were detected by immunohistochemistry(IHC).RESULTS The tumor volume,tumor weight and lung metastases of mice in the shRNA group were significantly decreased than those in the NC group,and their survival time was longer than that of the NC group.Following combined treatment with nab-PTX and anti-PD-1 antibody,the shRNA group mice demonstrated the slowest tumor growth(P＜0.05),the lowest relative tumor weight(P＜0.05),and the lowest Ki67 expression level(P＜0.05)among all groups.Mice in the 740 Y-P group exhibited the most rapid tumor volume increase(P＜0.05),and the highest levels of phosphorylated PI3K and AKT in tumor tissues(P＜0.05).There were no statistically significant differences in tumor volume,tumor weight,Ki67 expression level and the phosphorylation level of PI3K/AKT protein between shRNA+combined treatment group and shRNA+nab-PTX+740 Y-P group as well as the shRNA+anti-PD-1 antibody+740 Y-P group(P＞0.05).Both the Serpincl gene knockdown and the combination treatment could inhibit the expression of TLR4 in tumor tissues,and the phosphorylation level of NF-κB was significantly increased after the administration of 740 Y-P,while the expression of TLR4 was not significantly changed.CONCLUSION The Serpinc1 gene may regulate the PI3K/AKT signaling pathway through TLR4 to enhance the efficacy of nab-PTX combined with anti-PD-1 antibody in lung cancer treatment.关键词
肺癌/Serpinc1基因/白蛋白结合型紫杉醇/PD-1抗体/联合治疗/PI3K/AKT信号通路Key words
lung cancer/Serpinc1 gene/albumin-bound paclitaxel/anti-PD-1 antibody/combination treatment/the PI3K/AKT signaling pathway分类
药学引用本文复制引用
张君,郝文婧,王云霞,蔡卫民..Serpinc1基因通过调控PI3K/AKT信号通路增强白蛋白结合型紫杉醇联合程序性死亡受体-1抗体的抗肺癌效果[J].中国临床药学杂志,2025,34(1):1-9,9.基金项目
国家自然科学基金(编号8217130423) （编号8217130423）
