医学分子生物学杂志2026，Vol.23Issue(2)：164-170,7.DOI:10.3870/j.issn.1672-8009.2026.02.008
MMP2调节高级别浆液性卵巢癌细胞对PARP抑制剂Olaparib敏感性的机制研究
Effect of MMP2 Expression on Cell Sensitivity to PARP Inhibitor Olaparib in High-grade Serous Ovarian Cancer Cells
摘要
Abstract
Objective To investigate the effect of matrix metalloproteinase 2(MMP2)on the sensitivity of poly-ADP ribose polymerase inhibitor(PARPi)in high-grade serous ovarian cancer(HGSOC)cells and the underlying mechanism.Methods The HGSOC cell line HeyA8 cells were divided into 3 groups:control group,sh-NC group,sh-MMP2 group.RT-qPCR and Western blot-ting were used to detect the expression of MMP2.CCK-8 method was used to detect the cell survival rate under different concentrations of Olaparib.Then HeyA8 cells were divided into 4 groups:sh-NC group,sh-MMP2 group,sh-NC+PARPi group,sh-MMP2+PARPi group.Wound-healing assay,Annexin V-FITC/PI method and Hochest 33258 staining were used to detect cell migration and ap-optosis,respectively.Western blotting was used to determine the expression levels of proteins related to the vascular endothelial growth factor(VEGF)/phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt).Results Compared with those in the control group and the sh-NC group,the relative expression levels of MMP2 mRNA and protein of HeyA8 cells in the sh-MMP2 group were downregulated,and the cell survival rate after Olaparib treatment was reduced(P<0.05).Com-pared with those in the sh-NC group,the wound-healing rate of HeyA8 cells in the sh-MMP2 group was decreased,the apoptosis rate was increased,nuclear condensation and fragmentation of apop-totic cells were observed,the relative protein expression levels of vascular endothelial growth factor A(VEGFA),vascular endothelial growth factor receptor 2(VEGFR-2),phosphorylated PI3K(Tyr458)[p-PI3K(Tyr458)]and phosphorylated Akt(Ser473)[p-Akt(Ser473)]were all downregulated(P<0.05).Compared with those in the sh-NC+PARPi group,the wound-healing rate of HeyA8 cells in the sh-MMP2+PARPi group was decreased,the apoptosis rate was in-creased,more apoptotic cells with nuclear condensation and fragmentation were observed,the rela-tive protein expression levels of VEGFA,VEGFR2,p-PI3K(Tyr458)and p-Akt(Ser473)were downregulated(P<0.05).Conclusion Silencing MMP2 expression can promote PARPi-induced apoptosis in HGSOC cells,and increase PARPi sensitivity.关键词
高级别浆液性卵巢癌/基质金属蛋白酶2/奥拉帕尼/药物敏感性/血管内皮生长因子/磷脂酰肌醇3-激酶/蛋白激酶B通路Key words
high-grade serous ovarian cancer/matrix metalloproteinase 2/olaparib/drug sensitivity/vascular endothelial growth factor/phosphatidylinositol 3-kinase/pro-tein kinase B pathway分类
医药卫生引用本文复制引用
邵萍,邓青春..MMP2调节高级别浆液性卵巢癌细胞对PARP抑制剂Olaparib敏感性的机制研究[J].医学分子生物学杂志,2026,23(2):164-170,7.基金项目
海南省自然科学基金高层次人才项目(No.821RC712) This work was supported by a grant from the High-level Talent Program of Natural Science Foundation in Hunan(No.821RC712) （No.821RC712）
