Abstract:

Objective To investigate the role and underlying mechanism of nicotinamide （NAM） in promoting 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 analyze 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 formation， wound healing， and Transwell assays were conducted to evaluate cervical cancer cell proliferation， migration， and invasion capacities. Results Clinical sample analysis revealed that both NAMPT and PD-L1 were significantly upregulated in cervical cancer tissues compared to adjacent normal tissues （P < 0.05）. In vitro experiments 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.

Key words: cervical cancer, NAMPT/NAD⁺, PD-L1, nicotinamide, malignant phenotype of tumor cells