Effects of magnolin and chloroform parts of Flos Magnoliae on gene expression in NCI-H1975 cells,and genetic changes after EGFR TKI resistance
we demonstrated that N-Myc Downstream Regulated 1 (NDRG1) interacts with and restrains Neuregulin 2 (NRG2) to down-regulate the EGFR. This inhibition prevents excessive autophagy protection, thereby reducing EGFR TKI drug resistance in lung cancer cell lines and xenograft mouse models. Activation of NDRG1 using compounds like Chinese herb extract Flos Magnoliae and its active monomer (magnolin) restored sensitivity in resistant cell lines to EGFR TKIs and delayed resistance in lung cancer xenograft mice. These findings highlight a mechanism for resistance to a molecularly targeted therapy and provide a potential therapeutic target for overcoming resistance to EGFR TKIs, including the second-generation inhibitor afatinib Overall design: To investigate the genetic changes after EGFR TKI resistance and to find the inhibitors of resistance genes