ZHANG Liang,YANG Jiaqi,ZHANG Teming, et al. Polo-like kinase 4 inhibitor Centrinone affects the proliferation and apoptosis of gastric cancer cells byregulating PI3K/AKT pathway[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2023, 53(11): 881-888.
Abstract：Objective: To investigate the effect of Centrinone on the proliferation, migration and apoptosis of gastric cancer cells and its anti-cancer mechanism. Methods: The expression of polo-like kinase 4 (PLK4) gene in gastric cancer and adjacent tissues and its effect on prognosis were analyzed in the TCGA database. The localization of PLK4 in gastric cancer tissues was analyzed in Human Proteome Atlas. Different gastric cancer cell lines were treated with different concentrations of Centrinone (0, 1, 2, 5 μmol/L), and the cell growth was detected by CCK8 method. Transwell chamber was used to detect the effect of Centrinone on the migration ability of AGS cells. The apoptosis of AGS cells was detected by flow cytometry. The apoptosis-related proteins such as poly ADP-ribose polymerase (PARP), Caspase 3, BCL-2, BAX, were detected by Western blot. Results: The expression of PLK4 in gastric cancer from TCGA database was significantly higher than that in para-cancer tissues (P<0.05), and was correlated with the prognosis of gastric cancer (P=0.001). Centrinone significantly inhibited the growth of AGS, BGC and SGC, and AGS was the most sensitive (IC50=1.386 μmol/L). The migration assay showed the higher the concentration of Centrinone, the less the number of gastric cancer cells migrated (P<0.05).Flow cytometry showed that the higher the concentration of Centrinone, the higher the percentage of apoptosis(P<0.05). Western blot results showed that with the increase of Centrinone concentration, the cleavage expression of apoptosis-related proteins PARP and caspase 3 increased (P<0.05), and the expression of BCL-2 decreased (P<0.05), while the protein expression of BAX did not change significantly (P>0.05). Phosphorylated protein expression levels of PI3K and AKT were significantly decreased (P<0.05). Conclusion: PLK4 inhibitor Centrinone can significantly inhibit the proliferation, migration and induce apoptosis of gastric cancer cells,possibly by inhibiting the expression of BCL-2 and regulating the PI3K/AKT signaling pathway.
