Cucurbitacin B Regulates Mitochondrial Apoptosis Through the NAMPT-FoxO3a Axis to Affect the Biological Function of Non-small Cell Lung Cancer Cells
10.3870/j.issn.1672-0741.25.03.020
- VernacularTitle:葫芦素B通过NAMPT-FoxO3a轴调控线粒体依赖性凋亡影响非小细胞肺癌细胞生物学行为
- Author:
Nan QIU
1
;
Yuhong REN
;
Jiafu LIU
Author Information
1. 福建省福州肺科医院病理科,福州 350008
- Publication Type:Journal Article
- Keywords:
cucurbitacin B;
nicotinamide phosphoribosyltransferase;
mitochondrial dependent apoptosis;
non-small cell lung cancer
- From:
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
2025;54(5):626-634
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the molecular mechanisms by which cucurbitacin B(CuB)regulates the mitochondrial ap-optosis pathway through the nicotinamide phosphoribosyltransferase(NAMPT)/forkhead transcription factor O subfamily member 3a(FoxO3a)axis to affect the biological function of non-small cell lung cancer(NSCLC)cells.Methods Gefitinib(GEF)and CuB were used to intervene in A549 cells.Network pharmacology was employed to analyze the targets and downstream pathways,and different vector-transfected cell groups were set up.Cell viability was detected by CCK-8 assay,cell invasion by Transwell assay,and cell apoptosis by flow cytometry.The mitochondrial membrane potential(MMP)level was measured using a JC-1 kit,and intracellular reactive oxygen species(ROS)levels were detected using a kit.Western blot was used to detect the expression of mitochondrial dynamics-related proteins(DRP1,Mfn1),as well as the protein levels of NAMPT and FoxO3a in A549 cells.The mRNA expression of NAMPT was detected by qRT-PCR.Additionally,a xenograft model in nude mice was es-tablished to verify the therapeutic effects of CuB in vivo.Results Compared with the control group,GEF and CuB intervention significantly inhibited the viability and invasion of A549 cells and induced cell apoptosis.Moreover,CuB intervention significant-ly decreased the MMP level,increased ROS concentration,and upregulated the expression of DRP1 while downregulating Mfn1 in A549 cells(P＜0.05).NAMPT,a therapeutic target,was highly expressed in A549 cells and was inhibited by CuB.Compared with the vector group,overexpression of NAMPT significantly promoted the growth of A549 cells and inhibited mitochondrial apoptosis.Compared with the vector+CuB(100 nmol/L)group,overexpression of NAMPT reversed the effects of CuB on A549 cells(P＜0.05).Compared with the si-NAMPT-NC group,silencing NAMPT significantly inhibited the growth of A549 cells and promoted mitochondrial apoptosis,while knockdown of FoxO3a enhanced the viability and invasion of A549 cells and re-versed the damaging effects of si-NAMPT on cancer cells(P＜0.05).In vivo experimental results showed that CuB inhibited tumor weight and volume in a dose-dependent manner.Conclusion CuB regulates the NAMPT-FoxO3a axis through the mito-chondrial apoptosis pathway to inhibit the progression of NSCLC both in vitro and in vivo.
