Modulation of autophagy and apoptosis can contribute to the anticancer effect of Abemaciclib/Celecoxib combination in colon cancer cells

Abstract

AbstractDrug resistance and recurrence represent a great challenge in colorectal cancer management, highlighting the urgent need for novel therapeutics. Our objective is to evaluate the influence of Abemaciclib, Celecoxib, and their combination on both the autophagic and apoptotic machinery in an attempt to unravel the interplay between them in HCT-116 and Caco-2 cell lines. The MTT assay was used to assess the GI50 of the drugs. ELIZA was used to determine the protein levels of Beclin-1, LC3, Cox-2, and Bcl-2. Active Caspase-3 was determined by a colorimetric assay. Gene expression levels of ATG5, LC3, Beclin-1, and p62 were assessed by quantitative real-time PCR. In HCT-116 cells, the GI50s for Abemaciclib and Celecoxib were 15.86 and 92.67 μM, respectively, while for Caco-2 cells, the GI50s were 7.85 and 49.02 μM for Abemaciclib and Celecoxib, respectively. Upon treatment of HCT-116 and Caco-2 cells with Abemaciclib, Celecoxib, and their combinations, ATG5, p62, LC3, and Beclin-1 gene expression levels were up-regulated. The protein levels of Beclin-1, LC3, and Caspase-3 were significantly increased, while Bcl-2 was decreased in both cell lines due to single and combined treatments. Both drugs, either alone or in combination, decreased the migration ability of the cells in both cell lines. To conclude, the treatment protocol has the potential to induce cell cycle arrest, diminish the potentiality of cells for migration, and initiate apoptotic and autophagic cell death. Further research is recommended to unravel the potential antitumor effects of Abemaciclib/Celecoxib combination in different cancer types.