Knockdown of Inhibin Beta A Reversed the Epithelial Growth Factor Receptor Tyrosine Kinase Inhibitor Resistance and Enhanced the Therapeutic Effect of Radiotherapy in Non-Small Cell Lung Cancer

Lung cancer is a malignant tumor with the highest mortality rate worldwide. Non-small cell lung cancer (NSCLC) accounts for approximately half of all lung cancer cases. Inhibin beta A (INHBA) is a ligand of the transforming growth factor-beta superfamily. This study aimed to analyze the function of INHBA in NSCLC resistance cells. Gene Expression Omnibus and The Cancer Genome Atlas databases were used to identify differentially expressed genes (DEGs) in NSCLC resistance cells and patients. DEGs were further analyzed by gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis. A colony formation assay was performed to determine cell growth. Cell migration and invasion were tested by Transwell assay. Epithelial-mesenchymal transition (EMT)-related genes were analyzed using qRT-PCR and Western blot analysis. Using bioinformatics tools, INHBA was demonstrated to be overexpressed in NSCLC resistant cells and patients. Gefitinib treatment affected NSCLC resistant cells. Additionally, INHBA silencing or X-ray treatment suppressed the growth and metastasis of NSCLC resistant cells. Moreover, the combined application of INHBA silencing and X-ray treatment enhances the therapeutic effects. Moreover, EMT has been confirmed to occur in NSCLC resistant cell lines. Both INHBA silencing and X-ray treatment inhibited EMT development. This study demonstrated that INHBA silencing ameliorates EGFR-TKI resistance and enhances the therapeutic effect of radiotherapy in NSCLC.