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

Abstract

Formononetin is one of the main isoflavone components, which has strong anti-cancer effects in non-small cell lung cancer (NSCLC). However, the potentials and the mechanisms of Formononetin to counteract the Osimertinib resistance in NSCLC are unclear. In this study, Formononetin-induced cell apoptosis, cell proliferation, and clonal formation were detected in Osimertinib-resistant NSCLC cells (H1975_OR). RNA sequencing analysis was conducted to study the gene expression profiles of Formononetin-induced H1975_OR cells. The results indicated that Formononetin could significantly induce cell apoptosis, whereas dramatically inhibited cell proliferation and clonal formation on H1975_OR cells. Furthermore, a total of 4309 differentially expressed genes (DEGs) between Formononetin-treated and nontreated H1975_OR cells were had been detected. Gene Ontology (GO) annotation enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and the Gene Set Enrichment Analysis (GSEA) showed that Formononetin affected the expression of genes involving in anatomical structure morphogenesis, anatomical structure development, and multicellular organism development via regulating inflammation- and metabolism-related signaling pathways. Taken together, our study preliminarily revealed the mechanisms of Formononetin to counteract the Osimertinib resistance in NSCLC cells from the transcriptional level and provided a potential treatment method for Osimertinib-resistant NSCLC patients.