Mechanisms analysis for Formononetin counteracted-Osimertinib resistance in Non-small-cell lung cancer cells: from the insight into the gene transcriptional level

Backgrounds: Osimertinib resistance in Non-Small-Cell Lung Cancers (NSCLC) is a difficult problem to be solved in clinic. Formononetin is one of the main isoflavone components, which has strong anti-cancer effects in NSCLC. However, the potential effects and the mechanisms of Formononetin to counteract the Osimertinib resistant in NSCLC is remain to be uncovered. Methods: Osimertinib-resistant NSCLC cell line (H1975_OR) was generated by increasingly adding of Osimertinib in H1975 cell culture medium. The Formononetin was used to induce H1975_OR cell apoptosis an to inhibit cell proliferation and clonal formation. The RNA-sequencing was used to study the potential mechanisms for Formononetin to counteract the Osimertinib resistant in NSCLC. Results: Formononetin could significantly induced cell apoptosis, whereas, dramatically inhibited cell proliferation and clinal formation in H1975_OR cells. Formononetin induced tremendous alterations of gene expression in H1975_OR cells and these genes can be clustered into unique GO, KEGG and GSEA pathways. Conclusion: Our results preliminarily uncovered the underlying mechanisms for Formononetin counteracted Osimertinib-resistance in NSCLC cells and provided a potential treatment method for Osimertinib resistant NSCLC patients. Keywords: Osimertinib-resistant NSCLC, Formononetin, Cell apoptosis, RNA-sequencing