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

doi:10.3969/j.issn.1006-5725.2026.09.007

摘要/Abstract

摘要：

目的探讨烟酰胺（nicotinamide，NAM）通过激活NAMPT/NAD?代谢轴调控程序性死亡配体1（programmed death-ligand 1，PD-L1）表达、并促进宫颈癌恶性进展的作用机制。方法利用30例配对宫颈癌及癌旁组织分析烟酰胺磷酸核糖基转移酶（nicotinamide phosphoribosyltransferase，NAMPT）和PD-L1在宫颈癌中的表达；qRT-PCR、Western blot检测NAMPT、PD-L1转录及蛋白表达水平；采用NAMPT抑制剂（FK866）抑制NAMPT表达，验证其在代谢—免疫调控中的关键作用；通过CCK-8法、克隆形成实验、划痕实验、Transwell实验评估宫颈癌细胞增殖、迁移及侵袭能力。结果临床样本验证显示，NAMPT、PD-L1在宫颈癌组织中高表达（P < 0.05）；体外细胞实验示，外源性NAM处理可浓度依赖性上调宫颈癌细胞中NAMPT、PD-L1的表达（P < 0.05），并显著增强其增殖、迁移及侵袭能力（P < 0.05）；而FK866可特异性阻断NAM的上述效应（P < 0.05），且逆转PD-L1的上调表达。结论 NAM激活NAMPT/NAD?代谢轴，上调PD-L1表达并促进肿瘤细胞恶性生物学行为；二者在该轴调控下同步变化，提示存在潜在内在调控关联。

关键词: 宫颈癌, NAMPT/NAD?, 程序性死亡配体1, 烟酰胺, 肿瘤细胞恶性表型

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

中图分类号:

R737.33

唐倩云,陆欣怡,陈钰,许涵洁,陈道桢. 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[J]. 实用医学杂志, 2026, 42(9): 1536-1544.

Qianyun TANG,Xinyi LU,Yu CHEN,Hanjie XU,Daozhen CHEN. Nicotinamide promotes cervical cancer progression via the NAMPT/NAD⁺ axis-mediated regulation of PD-L1[J]. The Journal of Practical Medicine, 2026, 42(9): 1536-1544.

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基因名称	引物序列
NAMPT	上游：5'-TAAAAGCTGTTCCTGAGGGCT-3'
NAMPT	下游：5'-AGAATTTGTGGCCACTGTGATTG-3'
PD-L1	上游：5'-CTGCTTGTCCAGATGACTTCGG-3'
PD-L1	下游：5'-CTGGTTGATGGTCTTGTGGTTG-3'
β-actin	上游：5'-TCCATCATGAAGTGTGACGT-3'
β-actin	下游：5'-GAGCAATGATCTTGATCTTCAT-3'

组别	细胞克隆数/个	24 h细胞迁移面积比	细胞迁移数/个	细胞侵袭数/个
Ctrl组	136.67 ± 20.50	1.00 ± 0.14	213.33 ± 15.14	207.67 ± 12.10
NAM组	294.67 ± 10.07	1.23 ± 0.15	321.00 ± 19.67	545.00 ± 51.68
t值	11.98	2.88	7.51	11.01
P值	0.000	0.024	0.002	0.000

组别	细胞克隆数/个	24 h细胞迁移面积比	细胞迁移数/个	细胞侵袭数/个
Ctrl组	184.00 ± 15.52	1.00 ± 0.12	254.33 ± 28.04	262.33 ± 20.66
NAM组	329.33 ± 26.41^*	1.76 ± 0.24^*	583.33 ± 8.14^*	619.33 ± 26.08^*
NAM + FK866组	186.33 ± 15.89^#	1.27 ± 0.20^#	297.67 ± 27.10^#	216.00 ± 6.08^#