الفهرس | يوجد فقط 14 صفحة متاحة للعرض العام |
المستخلص This study was designed to explore the expected role of colon cancer stem cells (CSCs) during the chemicallyinduced mouse colon carcinogenesis with/or without the treatment with a targeted therapeutic (anti-COX-2) drug, celecoxib. Two experiments were performed, the first, a short term 16- week colon carcinogenesis bioassay and the other was a 32- week colon cancer bioassay. Celecoxib treatment has lowered the numbers of aberrant crypt foci (ACF), the well known biomarker of colon carcinogenesis, as well as the tumors’ volumes and multiplicities. The immunohistochemical proliferating cell nuclear antigen (PCNA) labeling indexes LI (%) were down-regulated after treatment by Celecoxib. Also, the expression patterns of CD133and CD44, known to be associated with CSCs, showed differential expression patterns depending on the stage of carcinogenesis and celecoxib treatment. The flow cytometric analysis revealed that the number of CD133 cells was increased in the colonic epithelium of mice after 16weeks, however, the number of CD44 but not CD133 cells was increased after 32 weeks. Moreover, the Aldehyde dehydrogenase-1 activity levels, a known CSC marker in colonic epithelium, was down-regulated after 16 weeks, but up-regulated after 32 weeks. The data have also shown that celecoxib has modulated the mRNA expression levels of APC and COX-2 genes, which are directly related to colon cancer. Thus, the specific markers and CSC populations targeted by this drug may vary depending on the genetic and phenotypic stages of carcinogenesis. This could be useful during specific treatment and targeted therapy for colon cancer patients. Key words: Colon cancer, ACF, mice, 1,2- Dimethylhydrazine, cancer stem cells, ALDH1, CD44, CD133, PCNA, COX-2, APC. |