The effect of the iron chelator Deferasirox in combination with Cisplatin chemotherapy against lung carcinoma

Abstract

The preferred treatment for patients with lung carcinoma (LC) is platinum‐based regimens, eg., Cisplatin (CisPt). Unfortunately, despite improvements in LC outcomes, many of these tumors metastasize and develop resistance against such Pt‐drugs, inducing abysmally low survival prognosis. Due to this, there is an urgent need to develop alternative therapies for LC mostly focused on overcome or diminish chemoresistance and inhibit the metastatic spread. FDA‐approved drugs which target cancer metabolic pathways are considered as repurposing drugs that could diminish these adverse effects. Deferasirox (Def), an FDA‐approved iron chelation therapy, is a drug under study for cancer therapy due to iron plays a key role in cell growth and energy production in cancer. Herein, we determined the effect of deferasirox (Def) alone and in combination with CisPt on the genes related to chemoresistance and metastasis in LC cells. Viability assay results showed that Def has synergistic cytotoxic effects in combination with CisPt after 24 h of incubation in A549 LC cells. qPCR gene expression studies showed that Def induced a significant downregulation of EGFR, VEGF, MMP9, Pgp, P53, NDRG1, CHD4 genes in A549 cells. In addition, we determined that Def induce the production of reactive oxygen species in LC. Furthermore, in in vivo studies performed in Lewis Lung Carcinoma mouse model, Def co‐administered with CisPt showed tumor size reduction. The results obtained from this study will impact the field of lung cancer therapy adding knowledge on the Def cellular mechanisms and genetic regulation against chemoresistance and metastasis processes.