The effect of magnetic nanoparticles containing hyaluronic acid and methotrexate on the expression of genes involved in apoptosis and metastasis in A549 lung cancer cell lines

Abstract

Lung cancer has been shown to be resistant to treatment with some chemotherapy drugs due to epithelial-mesenchymal transmission (EMT). Because the rate of cytotoxicity and induction of apoptosis by methotrexate (MTX) is negligible in A549 lung cancer cells, a CD44 positive cell line, we decided to synthesize magnetic nanoparticles (MNPs) containing hyaluronic acid (HA) and MTX to evaluate the effect of CD44 receptor targeting on the expression of genes involved in apoptosis. The TNF genes can modulate the expression of CD44 and implicate carcinogenesis and metastases. Therefore, inhibition of the TNF gene and study of its interaction with the CD44 receptor can determine the success of a treatment method. The results of the MTT assay confirmed that the MNPs-HA-MTX offered better cellular cytotoxic effects on cell viability than free MTX. The real-time PCR test also showed that the Bak1/Bclx ratio was 52.5 times higher than the control. On the other hand, the expression of the TNF gene was severely reduced, which could be due to the binding of HA-moiety of the MNPs-HA-MTX to the receptor and endocytosis. All the results gave us hope that we could increase the effectiveness of methotrexate in lung cancer by targeting the CD44 receptor.

Keywords

• Drug delivery
• TNF
• Bak1/Bclx ratio
• CD44 receptor
• Cancer therapy
• Caspase-3