The Anti-tumor Activity Of Small Molecule Inhibitor Of AZIN In Non-small Cell Lung Cancer A549

Objective Targeted drugs can significantly improve the survival time and quality of life of patients with non-small cell lung cancer.In this study,we used ornithine decarboxylase antizyme inhibitor-1（AZIN-1）in the autoregulatory circuit of ornithine decarboxylase（ODC）as a target to computer-assisted screen small molecule inhibitors and investigated the inhibitory effect and mechanism of AZIN-1 small molecule inhibitors on non-small cell lung cancer A549 cells.Methods 1)The inhibitory effect of small molecule inhibitors on the growth of A549cells was detected by Cell Counting Kit-8（CCK-8）assay;2)The apoptotic effect of small molecule inhibitors on A549 cells was analyzed by flow cytometry（Annexin V-FITC/PI double staining）;3)The effect of small molecule inhibitors on A549 cell cycle was analyzed by flow cytometry（PI single staining）;4)Cell migration was detected by cell scratch assay;5)Total polyamine content in A549 cells was measured by high-performance liquid chromatography（HPLC）;6)The expression of ODC,ornithine decarboxylase antizyme-1（AZ-1）and AZIN-1 in A549 cells was detected by Western blot.Results 1)No.19 drug,a small molecule inhibitor targeting AZIN-1,significantly inhibited the proliferation of A549 cells,while drug 22 had no significant inhibitory effect on cell proliferation;2)No.19 drug was able to promote apoptosis in A549 cells,while No.22 drug had no significant effect on apoptosis;3)No.19 drug arrested A549 cells in G₀/G₁phase,while No.22 drug had no significant effect on cell cycle;4)No.19 drug significantly inhibited the migration of A549 cells at 12 h and 24 h,while No.22 drug had no significant effect on the migration of A549 cells;5)No.19 drug was able to completely inhibit the production of putrescine in A549 cells and was ultimately able to reduce the content of total intracellular polyamines,while No.22 drug had no significant effect on intracellular polyamine levels;6)No.19 drug significantly decreased the content of AZIN-1 and ODC in A549 cells,and increased the content of AZ-1,while No.22 drug had no significant effect on the content of AZIN-1,ODC and AZ-1 in A549 cells.Conclusion The results of this study demonstrate that AZIN-1 small molecule inhibitor No.19 drug could significantly inhibit the proliferation of A549 cells,cause G₀/G₁cycle arrest,induce apoptosis,and inhibit cell migration,significantly inhibit the expression of AZIN-1 and ODC,and reduce the total intracellular polyamine content.The above results indicate that No.19 drug provides a new idea for the research and development of anti-non-small cell lung cancer targeted drugs.