salinomycin and Adenomatous-Polyposis-Coli

This field trial was designed to investigate whether the incorporation of zinc bacitracin into pig feed would prevent porcine intestinal adenomatosis. Two hundred-and-eighty-eight weaned pigs on a farm with a previous history of the disease were divided into 16 pens of 18 pigs. Two dietary regimens of zinc bacitracin were tested: from weaning up to 100 days of age, either 300 or 200 ppm zinc bacitracin were incorporated; from 100 to 125 days of age, either 200 or 100 ppm zinc bacitracin were added; and from 125 to 156 days of age (slaughter), either 100 or 50 ppm zinc bacitracin were added. The results were compared with a positive control group which received 60, 60 and 30 ppm salinomycin during the same periods, and with a negative control group which received no antibacterial and/or performance enhancer. The mortality, diarrhoea scores, average daily weight gains, average daily feed intakes and feed conversion ratios of the pigs were assessed. At slaughter, samples of ileum were taken from eight randomly selected pigs per group for bacteriological and histopathological examinations. The three treated groups all performed better than the control group, and the group receiving the high dose regimen of zinc bacitracin performed significantly better than the groups receiving the low dose of zinc bacitracin or salinomycin.

Topics: Adenomatous Polyposis Coli; Animal Feed; Animals; Anti-Bacterial Agents; Bacitracin; Diarrhea; Dose-Response Relationship, Drug; Female; Ileal Neoplasms; Ileum; Male; Pyrans; Swine; Swine Diseases

Colorectal cancer (CRC) is one of the most common cancers worldwide, in which adenomatous polyposis coli (APC) mutations are frequently and uniquely observed. Here we find that cis-HOX (circular RNA stabilizing HOXC10) is robustly expressed in colorectal tumor-initiating cells (TICs). cis-HOX knockout decreases colorectal TIC numbers and impairs the self-renewal, tumorigenesis, and metastatic capacities of TICs, whereas cis-HOX overexpression drives colorectal TIC self-renewal and metastasis. Mechanistically, cis-HOX binds to HOXC10 mRNA to attenuate its decay through blocking the K-homology splicing regulatory protein (KSRP)-binding sequence of HOXC10 3' UTR. HOXC10 is highly expressed in colorectal tumors and TICs and triggers Wnt/β-catenin activation by activating FZD3 expression. HOXC10 inhibitor salinomycin exerts efficient therapeutic effects in APC-wild-type colorectal tumors, but not in tumors with APC nonsense mutations. Therefore, the cis-HOX-HOXC10 pathway drives colorectal tumorigenesis, stemness, and metastasis and serves as a potential therapeutic target for APC-wild-type colorectal tumors.

Topics: Adenomatous Polyposis Coli; Aged; Aged, 80 and over; Animals; Carcinogenesis; Cell Line, Tumor; Cell Self Renewal; Colorectal Neoplasms; Female; Frizzled Receptors; Gene Expression Regulation, Neoplastic; Homeodomain Proteins; Humans; Male; Mice, Knockout; Molecular Targeted Therapy; Mutation; Neoplastic Stem Cells; Pyrans; RNA Stability; RNA-Binding Proteins; RNA, Circular; RNA, Messenger; Wnt Signaling Pathway