Targeting NAD + biosynthesis suppresses TGF-β1/Smads/RAB26 axis and potentiates cisplatin cytotoxicity in non-small cell lung cancer brain metastasis.

ABSTRACT: Nicotinamide adenine dinucleotide (NAD⁺) plays an important role in tumor progression, but its role in non-small cell lung cancer with brain metastasis (NSCLC BM) remains unclear. Herein, we investigated NAD⁺ biosynthesis targeting as a new therapeutic strategy for NSCLC BM. Therapeutic activity of nicotinamide phosphoribosyl transferase (NAMPT) inhibitors was evaluated in mouse models of NSCLC BM and using various assays such as NAD⁺ quantitation, cell viability, and apoptosis assays. To explore impact on downstream signaling, RNA sequencing was used in NAMPT inhibitor-treated and control cells, followed by validation with genetic knockdown, western blot and qRT-PCR. Expression of NAMPT and downstream proteins in human NSCLC BM and its association with pat

SUBMITTER: Zhou L 

PROVIDER: S-EPMC11895195 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature