{Reference Type}: Journal Article
{Title}: Protective effects of palbociclib on colitis-associated colorectal cancer.
{Author}: Yang L;Gao J;Zhang Y;Perez EA;Wu Y;Guo T;Li C;Wang H;Xu Y;
{Journal}: J Gastrointest Oncol
{Volume}: 14
{Issue}: 6
{Year}: 2023 Dec 31
{Factor}: 2.587
{DOI}: 10.21037/jgo-23-860
{Abstract}: <B>UNASSIGNED: </B>Chronic or recurrent inflammatory injury to the intestinal mucosa is closely related to inflammation-related colorectal cancer (CRC). This study aimed to examine the protective effects of palbociclib, a stimulator of interferon genes (STING) antagonist, on colitis-related colorectal carcinogenesis.<BR><B>UNASSIGNED: </B>Bioinformatic analyses, including Gene Ontology (GO) enrichment, gene set enrichment analysis (GSEA), and network analysis, were conducted. Male C57BL/6 mice were administered azoxymethane (AOM) and dextran sulfate sodium (DSS), followed by treatment with palbociclib for 6 weeks. The general conditions of mice were observed and recorded. The colon histopathology was assessed based on hematoxylin and eosin (H&E) staining results. Relative messenger RNA (mRNA) expression levels of interferon b1 (Ifnb1), interleukin 6 (Il6), and interleukin 1b (Il1b) in colon were estimated based on quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analysis.<BR><B>UNASSIGNED: </B>The STING signaling pathway was significantly upregulated in stages III and IV of CRC in The Cancer Genome Atlas (TCGA)-CRC cohort. After treatment with AOM/DSS, the weight of mice decreased significantly, whereas administration of palbociclib partially reversed this trend. The mouse colon treated with AOM/DSS showed significant pathological damages, disorderly epithelial cell structure, atypical hyperplasia, and infiltration of several inflammatory cell types; however, the colon damage was remarkably reduced upon treatment with palbociclib. It was also found that palbociclib almost abolished the increase in the downstream effectors of STING-mediated transcription in the colon tissue treated with AOM/DSS, as evidenced by the transcription levels of Ifnb1, Il6, and Il1b.<BR><B>UNASSIGNED: </B>These findings indicate that the STING pathway is closely associated with CRC. Palbociclib significantly alleviates tumor development in AOM/DSS-induced colitis-associated CRC.