[Aumolertinib inhibits proliferation, invasion and migration and promotes apoptosis of neuroblastoma cells by downregulating MMP2 and MMP9 expression]. 2023

X Liu, and Y Yang, and H Cai, and Y Zhang, and F Fan, and X Li, and S Li
School of Pharmacy, Bengbu Medical College, Anhui Provincial Engineering Technology Research Center of Biochemical Pharmaceuticals, Bengbu 233030, China.

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

UI MeSH Term Description Entries
D008819 Mice, Nude Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses. Athymic Mice,Mice, Athymic,Nude Mice,Mouse, Athymic,Mouse, Nude,Athymic Mouse,Nude Mouse
D009447 Neuroblastoma A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51) Neuroblastomas
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014746 Vimentin An intermediate filament protein found in most differentiating cells, in cells grown in tissue culture, and in certain fully differentiated cells. Its insolubility suggests that it serves a structural function in the cytoplasm. MW 52,000.
D015820 Cadherins Calcium-dependent cell adhesion proteins. They are important in the formation of ADHERENS JUNCTIONS between cells. Cadherins are classified by their distinct immunological and tissue specificities, either by letters (E- for epithelial, N- for neural, and P- for placental cadherins) or by numbers (cadherin-12 or N-cadherin 2 for brain-cadherin). Cadherins promote cell adhesion via a homophilic mechanism as in the construction of tissues and of the whole animal body. Cadherin,E-Cadherins,Epithelial-Cadherin,Liver Cell Adhesion Molecules,N-Cadherins,Neural Cadherin,P-Cadherins,Uvomorulin,Cadherin-1,Cadherin-2,Cadherin-3,E-Cadherin,Epithelial-Cadherins,Liver Cell Adhesion Molecule,N-Cadherin,Neural Cadherins,P-Cadherin,Placental Cadherins,Cadherin 1,Cadherin 2,Cadherin 3,Cadherin, Neural,Cadherins, Neural,Cadherins, Placental,E Cadherin,E Cadherins,Epithelial Cadherin,Epithelial Cadherins,N Cadherin,N Cadherins,P Cadherin,P Cadherins
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D051028 bcl-2-Associated X Protein A member of the Bcl-2 protein family and homologous partner of C-BCL-2 PROTO-ONCOGENE PROTEIN. It regulates the release of CYTOCHROME C and APOPTOSIS INDUCING FACTOR from the MITOCHONDRIA. Several isoforms of BCL2-associated X protein occur due to ALTERNATIVE SPLICING of the mRNA for this protein. Bax Protein,Bax-alpha Protein,Bax-omega Protein,Bax-sigma Protein,Bax Apoptosis Regulator Protein,Bax-beta Protein,Bax-delta Protein,bcl2-Associated X Protein,bcl2-Associated X Protein Isoform alpha,bcl2-Associated X Protein Isoform beta,bcl2-Associated X Protein Isoform delta,bcl2-Associated X Protein Isoform omega,bcl2-Associated X Protein Isoform sigma,Bax alpha Protein,Bax beta Protein,Bax delta Protein,Bax omega Protein,Bax sigma Protein,Protein, bcl-2-Associated X,X Protein, bcl-2-Associated,bcl 2 Associated X Protein,bcl2 Associated X Protein,bcl2 Associated X Protein Isoform alpha,bcl2 Associated X Protein Isoform beta,bcl2 Associated X Protein Isoform delta,bcl2 Associated X Protein Isoform omega,bcl2 Associated X Protein Isoform sigma

Related Publications

X Liu, and Y Yang, and H Cai, and Y Zhang, and F Fan, and X Li, and S Li
October 2020, Medical science monitor : international medical journal of experimental and clinical research,
X Liu, and Y Yang, and H Cai, and Y Zhang, and F Fan, and X Li, and S Li
January 2019, American journal of men's health,
X Liu, and Y Yang, and H Cai, and Y Zhang, and F Fan, and X Li, and S Li
January 2022, Mediators of inflammation,
X Liu, and Y Yang, and H Cai, and Y Zhang, and F Fan, and X Li, and S Li
September 2020, Drug development research,
X Liu, and Y Yang, and H Cai, and Y Zhang, and F Fan, and X Li, and S Li
March 2021, Reproductive biology,
X Liu, and Y Yang, and H Cai, and Y Zhang, and F Fan, and X Li, and S Li
February 2022, Oncology letters,
X Liu, and Y Yang, and H Cai, and Y Zhang, and F Fan, and X Li, and S Li
March 2009, Biochemistry,
X Liu, and Y Yang, and H Cai, and Y Zhang, and F Fan, and X Li, and S Li
September 2021, Experimental and therapeutic medicine,
X Liu, and Y Yang, and H Cai, and Y Zhang, and F Fan, and X Li, and S Li
August 2019, Journal of cellular biochemistry,
X Liu, and Y Yang, and H Cai, and Y Zhang, and F Fan, and X Li, and S Li
September 2019, Anti-cancer drugs,
Copied contents to your clipboard!