烟酰胺激活NAMPT/NAD+代谢轴调控程序性死亡配体1表达促进宫颈癌恶性进展的作用机制OA

Objective To investigate the role and underlying mechanism of nicotinamide(NAM)in pro-moting cervical cancer malignant progression and regulating PD-L1 expression via activation of the NAMPT/NAD+metabolic axis.Methods Thirty pairs of cervical cancer tissues and adjacent normal tissues were collected to ana-lyze the expression levels of nicotinamide phosphoribosyltransferase(NAMPT)and programmed death-ligand 1(PD-L1).Quantitative real-time polymerase chain reaction(qRT-PCR)and Western blotting were employed to quantify their transcriptional and protein levels,respectively.The specific NAMPT inhibitor FK866 was utilized to block NAMPT activity and verify its pivotal role in metabolic-immune regulation.Furthermore,CCK-8,colony for-mation,wound healing,and Transwell assays were conducted to evaluate cervical cancer cell proliferation,migra-tion,and invasion capacities.Results Clinical sample analysis revealed that both NAMPT and PD-L1 were sig-nificantly upregulated in cervical cancer tissues compared to adjacent normal tissues(P＜0.05).In vitro experi-ments demonstrated that exogenous NAM treatment upregulated NAMPT and PD-L1 expression in cervical cancer cells in a concentration-dependent manner(P＜0.05),while significantly enhancing cell proliferation,migration,and invasion(P＜0.05).Conversely,treatment with FK866 specifically abrogated these NAM-induced effects(P＜0.05)and reversed the upregulation of PD-L1.Conclusion NAM activates the NAMPT/NAD+metabolic axis to upregulate PD-L1 expression,thereby promoting the malignant biological behaviors of cervical cancer cells.The coordinated upregulation of NAMPT and PD-L1 suggests an intrinsic regulatory link within this metabolic-immune axis.