Pirfenidone sensitizes NSCLC cells to the antitumor effect of vinorelbine

Drug repurposing in cancer emerged as a strategy to identify antitumor potential in drugs clinically approved for the treatment of other diseases, offering new treatment possibilities especially for cancers with limited therapeutic alternatives, as the non-small cell lung cancer (NSCLC). Currently, vinorelbine, an anti-mitotic drug, is used for the treatment of NSCLC. The combination of vinorelbine with repurposed drugs that may increase its efficacy, with a tolerable safety profile, is an attractive therapeutic approach. Pirfenidone, an approved anti-fibrotic drug, has been previously demonstrated to sensitize different cancer cells to the effect of some anti-cancer agents. Therefore, our work aimed to assess the potential off-target effect of pirfenidone as a chemosensitizer of NSCLC cells to Vinorelbine.

Treatment of NCI-H460 NSCLC cells with pirfenidone enhanced the sensitivity of these cells to vinorelbine (determined with the Sulforhodamine B assay). This was verified in cells treated with the GI50 concentration of Pirfenidone (2mM) with the following concentrations of vinorelbine: 7nM (GI50), 3.5 nm and 1.75 nm. The strongest combination treatment increased the % of cells in the G1 phase of the cell cycle (determined by flow cytometry) and reduced cell proliferation (assessed with the BrdU assay). Importantly, the combined treatment (vinorelbine 7nM and pirfenidone 2mM) did not show toxicity in non-tumorigenic MCF10A cells.

Future work will validate these results in other cell lines and in xenograft mice models of NSCLC, to evaluate the possibility of repurposing pirfenidone for the treatment of NSCLC in combination with Vinorelbine approved regimens.