# Nickel Nanoparticles Promote Lung Adenocarcinoma Progression via CDK1-Mediated Fatty Acid Metabolism Regulation

## TL;DR

Nickel nanoparticles promote lung cancer progression by altering fatty acid metabolism through the CDK1/STAT3/FASN pathway, and apigenin may help block this effect.

## Contribution

This study is the first to link NiNPs to LUAD progression via the CDK1/STAT3/FASN axis and to propose apigenin as a potential inhibitor.

## Key findings

- NiNPs increase LUAD cell proliferation, migration, and EMT by activating the CDK1/STAT3/FASN axis.
- Genetic silencing of CDK1 or FASN reverses fatty acid metabolism dysregulation and reduces malignancy.
- Apigenin inhibits NiNP-induced tumor growth and blocks the CDK1/STAT3/FASN pathway in vitro and in vivo.

## Abstract

Nickel nanoparticles (NiNPs) are extensively used in nanotechnology, electronics, and biomedical fields, raising concerns about their pulmonary toxicity and potential role in inducing lung adenocarcinoma (LUAD). While heavy metals, like arsenic and cadmium, are well-known to drive LUAD through metabolic reprogramming, the molecular mechanism linking NiNPs to LUAD—particularly their impact on fatty acid metabolism (FAM)—remains unclear. This study is the first to explore whether NiNPs promote LUAD progression via the CDK1/STAT3/FASN axis, a key regulator of FAM, and to evaluate the natural compound apigenin (API) as a potential inhibitory agent. When human (A549) and mouse (LLC) LUAD cells were exposed to NiNPs, assessments of cell function and protein expression revealed increased malignant phenotypes, including enhanced proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT), along with activation of the CDK1/STAT3/FASN axis and upregulation of FAM-related markers. Genetic silencing of either CDK1 or FASN reversed the dysregulation of FAM and reduced the malignant characteristics of the cells. Molecular docking analysis confirmed that API binds strongly to CDK1, and further experiments demonstrated that API suppresses NiNP-induced tumor growth both in laboratory cell models and in living organisms, while also blocking the activity of the CDK1/STAT3/FASN axis.