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.