中国肿瘤生物治疗杂志2025，Vol.32Issue(8)：823-830,8.DOI:10.3872/j.issn.1007-385x.2025.08.005
扁蒴藤素经AKT/GSK-3β信号通路增强乳腺癌MCF-7细胞对多柔比星的敏感性
Pristimerin enhances the doxorubicin sensitivity of breast cancer MCF-7 cells via the AKT/GSK-3β signaling pathway
摘要
Abstract
Objective:To investigate the effect of pristimerin(PT)on doxorubicin(DOX)sensitivity of huamn breast cancer cell MCF-7 by regulating the protein kinase B(AKT)/glycogen synthase kinase-3β(GSK-3β)signaling pathway.Methods:MCF-7 cells were cultured in vitro and used to construct a DOX resistant cell line MCF-7/DOX.MCF-7 cells were separated into the NC group,the L-PT group(2 μmol/L PT),the M-PT group(4 μmol/L PT),the H-PT group(8 μmol/L PT),the H-PT+SC79 group(8 μmol/L PT+10 μmol/L AKT/GSK-3β signaling pathway inhibitor SC79),and the H-PT+LY294002 group(8 μmol/L PT+2.5 μmol/L AKT/GSK-3β signaling pathway activator LY294002).MCF-7/DOX cells were separated into the MCF-7/DOX group(untreated),the DOX group(50 nμmol/L DOX),PT+DOX group(8 μmol/L PT and 50 nμmol/L DOX),the PT+DOX+SC79 group(8 μmol/L PT+50 nμmol/L DOX+10 μmol/L SC79),and the PT+DOX+LY294002 group(8 μmol/L PT+50 nμmol/L DOX+2.5 μmol/L LY294002).MTT assay,plate cloning assay,scratch assay,Transwell assay,and WB assay were applied respectively to determine cell proliferation,colony formation,migration,invasion,and AKT/GSK-3β signaling pathway protein expression in each group.Establish a MCF-7 cell xenograft model in nude mice to observe the effects of PT on tumor growth and the protein expression of the AKT/GSK-3β signaling pathway in the tumor tissues.Results:Compared with the NC group,the proliferation rate,colony formation rate,scratch healing rate,invasive cell count,and the p-AKT,p-GSK-3β protein expressions of MCF-7 cells in the L-PT group,the M-PT group,and the H-PT group all showed a PT concentration dependent decrease(all P<0.05).Compared with the H-PT group,the trend of changes in the above indicators of MCF-7 cells in the H-PT+SC79 group was opposite to the above,while the trend of changes in the above indicators of MCF-7 cells in the PT+DOX+LY294002 group was the same(all P<0.05).There was no significant difference in the proliferation rate,colony formation number,scratch healing rate,invasive cell count,and expressions of p-AKT and p-GSK-3β proteins between the MCF-7/DOX group and the DOX group(all P>0.05).Compared with the MCF-7/DOX group and the DOX group,the PT+DOX group showed a decrease in the above indicators of MCF-7/DOX cells(all P<0.05).Compared with the PT+DOX group,the above indicators in the PT+DOX+SC79 group all increased,while the above indicators in the PT+DOX+LY294002 group all decreased(all P<0.05).Transplant tumor experiment in nude mice showed that compared with those in the control group and the DOX group,the mass and volume of transplant tumors,p-AKT and P-GSK-3β protein expressions in the PT+DOX group all decreased(all P<0.05).Conclusion:PT can inhibit the proliferation,migration,and invasion of BC cells,and enhance their sensitivity to DOX chemotherapy.,Its mechanism is related to the inhibition of the AKT/GSK-3β signaling pathway.关键词
扁蒴藤素/蛋白激酶B/糖原合成酶激酶-3β/乳腺癌/MCF-7细胞/化疗敏感性Key words
pristimerin(PT)/protein kinase B/glycogen synthase kinase-3β(AKT/GSK-3β)/breast cancer/MCF-7 cell/chemotherapy sensitivity分类
医药卫生引用本文复制引用
程超,王胄,张卫群..扁蒴藤素经AKT/GSK-3β信号通路增强乳腺癌MCF-7细胞对多柔比星的敏感性[J].中国肿瘤生物治疗杂志,2025,32(8):823-830,8.基金项目
新疆维吾尔自治区自然科学基金(No.2020D01C117) （No.2020D01C117）
