Atractyloside inhibits gefitinib‑resistant non‑small‑cell lung cancer cell proliferation

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Non-small cell lung cancer (NSCLC) presents a significant global health challenge with high mortality rates.
• Relapse in NSCLC is often driven by epidermal growth factor receptor mutations, complicating clinical treatment and necessitating novel therapeutic targets.
• Brother of the regulator of imprinted sites (BORIS), also known as CTCFL, is implicated in NSCLC progression and resistance to chemotherapy, including cisplatin and multidrug resistance.

Purpose of the Study:

• To investigate the role of BORIS expression in tyrosine kinase inhibitor (TKI)-resistant NSCLC cells.
• To evaluate the therapeutic potential of targeting BORIS in TKI-resistant NSCLC.
• To explore the anti-cancer effects of atractyloside on NSCLC cells, particularly in the context of TKI resistance.

Main Methods:

• Examined BORIS expression levels in TKI-resistant NSCLC cell lines.
• Utilized small interfering RNA (siRNA) to knockdown BORIS expression and assessed its impact on cell viability.
• Employed MTT assays to determine the effect of atractyloside on NSCLC cell proliferation.

Main Results:

• BORIS expression was analyzed in TKI-resistant NSCLC cells.
• Knockdown of BORIS using siRNA demonstrated an inhibitory effect on the viability of TKI-resistant NSCLC cells.
• Atractyloside treatment was found to inhibit the proliferation of TKI-resistant NSCLC cells, mimicking the effects of BORIS knockdown.

Conclusions:

• Inhibition of BORIS or its downstream pathways presents a potential therapeutic strategy for TKI-resistant NSCLC.
• Atractyloside effectively inhibits the proliferation of TKI-resistant NSCLC cells by regulating BORIS-related pathways.
• The findings support the investigation of atractyloside as a therapeutic agent for TKI-resistant NSCLC.