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

Abstract

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 (P<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 (P<0.01), up-regulated the expression levels of E-cadherin and Bax and lowered the expression levels of Bcl-2, vimentin, MMP2 and MMP9 (P<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.

• Authors: X Liu, Y Yang, H Cai, Y Zhang, F Fan, X Li, S Li
• Journal: Nan fang yi ke da xue xue bao = Journal of Southern Medical University (Nan Fang Yi Ke Da Xue Xue Bao) Vol. 43 Issue 9 Pg. 1493-1499 (Sep 20 2023) ISSN: 1673-4254 [Print] China
• PMID: 37814863 (Publication Type: English Abstract, Journal Article)

Chemical References

• aumolertinib
• Matrix Metalloproteinase 2
• Vimentin
• Matrix Metalloproteinase 9
• bcl-2-Associated X Protein
• Proto-Oncogene Proteins c-bcl-2
• Cadherins
• MMP2 protein, human
• MMP9 protein, human

Topics

• Animals
• Mice
• Humans
• Matrix Metalloproteinase 2
• Vimentin (pharmacology)
• Matrix Metalloproteinase 9
• Neuroblastoma (pathology)
• bcl-2-Associated X Protein
• Mice, Nude
• Cell Line, Tumor
• Cell Proliferation
• Apoptosis
• Proto-Oncogene Proteins c-bcl-2
• Cadherins