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

Abstract

BackgroundsOsimertinib 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. MethodsOsimertinib-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. ResultsFormononetin 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. ConclusionOur 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.