Inhibitory effect of gefitinib derivative LPY-9 on human glioma

The present study aimed to investigate the effects of a gefitinib derivative, LPY-9, on the proliferation, apoptosis and migration of human glioma cell line U251-MG by CCK8, Transwell or flow cytometry, and the effect of LPY-9 on the activity of caspase-3 enzyme and related proteins in the vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) pathways by western blot and ELISA. It was found that LPY-9 exhibited higher a inhibitory effect on the proliferation of U251-MG cell lines compared with gefitinib and it also exhibited a certain dose-dependence. Following LPY-9 treatment, typical apoptotic morphology was observed under the microscope after Giemsa staining. LPY-9 induced apoptosis at low concentration, and the activity of caspase-3 enzyme increased with the increase in drug concentration, significantly inhibiting the secretion of VEGF in a dose-dependent manner. The effect was notably more evident compared with gefitinib at the same concentration. The expression level of caspase-3 and cleaved caspase-3 increased with the increase in LPY-9 concentration; however, expression levels of VEGF, EGFR, phosphorylated AKT and PI3K decreased with the increase of LPY-9 concentration and no change was observed in the expression level of AKT. LPY-9 inhibited the proliferation of the human glioma cell line U251-MG, promoted apoptosis and effectively inhibited the migration of U251-MG cells. The effect of LPY-9 was more noticeable compared with gefitinib. The results of the present study may provide a foundation for further study and clinical research of this as an anti-tumor drug in animal models.