FNC inhibits non-small cell lung cancer by activating the mitochondrial apoptosis pathway

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• 4'-azid-2'-deoxy-2'-fluorarabinoside (FNC), a novel cytosine nucleoside analog, previously demonstrated significant anti-viral and anti-tumor activities.
• This study investigates the therapeutic potential and molecular mechanisms of FNC in non-small cell lung cancer (NSCLC).

Purpose of the Study:

• To explore the role and molecular mechanism of FNC in non-small cell lung cancer (NSCLC).
• To evaluate the efficacy and safety of FNC in preclinical NSCLC models.

Main Methods:

• FNC efficacy was assessed in NSCLC H460 cell line, Lewis mouse model, and H460 xenograft model.
• Cell viability, migration, invasion, and apoptosis were analyzed.
• Protein expression of key molecules involved in cell adhesion and invasion was evaluated using Western blot and IHC.

Main Results:

• FNC demonstrated time- and dose-dependent inhibition of H460 cell proliferation and metastasis.
• FNC treatment exhibited efficacy with low toxicity in both the Lewis mouse and H460 xenograft models.
• FNC induced apoptosis via mitochondrial pathway activation and inhibited invasion by modulating E-cadherin, VEGF, MMP-2, MMP-9, and CD31 expression.

Conclusions:

• FNC inhibits NSCLC progression by activating the mitochondrial apoptosis pathway.
• FNC regulates proteins involved in cell adhesion and invasion, underscoring its potential as an NSCLC therapeutic agent.