[Aumolertinib inhibits proliferation, invasion and migration and promotes apoptosis of neuroblastoma cells by downregulating MMP2 and MMP9 expression].

OBJECTIVE

To investigate the effects of aumolertinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), on biological behaviors of neuroblastoma SH-SY5Y cells.

METHODS

CCK-8 assay, colony-forming assay, Transwell assay and flow cytometry were used to assess the effects of 2, 4 and 8 μmol/L aumolertinib on proliferation, survival, migration, invasion and apoptosis of SH-SY5Y cells, and the changes in ultrastructure of the cells were observed using transmission electron microscopy. The protein expressions of Bax, Bcl-2, E-cadherin, vimentin, MMP2, and MMP9 in the treated cells were detected using Western blotting. A nude mouse model bearing subcutaneous SH-SY5Y cell xenograft were treated with aumolertinib (15 mg/kg) or cyclophosphamide (20 mg/kg), and the tumor volume and body mass changes was measured. HE staining was used to observe adverse effects of the treatment on the heart, liver, spleen, lungs and kidneys.

RESULTS

Aumolertinib significantly inhibited the proliferation and viability of SH-SY5Y cells (<0.05) with IC50 of 5.004, 3.728 and 3.228 µmol/L at 24, 48 and 72 h, respectively. Aumolertinib treatment induced obvious apoptosis of the cells, which showed characteristic morphological changes of apoptosis under transmission electron microscope. The treatment also inhibited the invasion and migration abilities of SH-SY5Y cells (<0.01), up-regulated the expression levels of E-cadherin and Bax and lowered the expression levels of Bcl-2, vimentin, MMP2 and MMP9 (<0.05). In the nude mouse models, treatment with aumolertinib effectively inhibited the growth of neuroblastoma without causing significant toxicity to the vital organs.

CONCLUSION

Aumolertinib inhibits proliferation, survival, invasion and migration and induces apoptosis in SH-SY5Y cells by downregulating MMP2 and MMP9 expression.