الفهرس 
Etiological factors of colon cancerOnly 14 pages are availabe for public view
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Abstract
The purpose of this study was to investigate the role of colon cancer stem cells (CSCs) during the chemically induced rat multi-step colon carcinogenesis with or without the treatment with a specific therapeutic drug (Cyclooxygenase-2 inhibitor; celecoxib). Two experiments were performed, the first,a short term- 12 week colon carcinogenesis bioassay in which only the surrogate markers for colon cancer; aberrant crypt foci (ACF) lesions were formed. The other experiment was a medium term colon cancer rat assay in which the tumors were formed after 32 weeks. Treatment with celecoxib has lowered the numbers of ACF, as well as the tumors volumes and multiplicities after 32 weeks. The immunohistochemical proliferating cell nuclear antigen (PCNA) labeling indexes LI (%) were down-regulated after treatment by celecoxib. Also the different cell surface antigens known to associate with CSCs such as the epithelial cell adhesion molecule (EpCAM), CD44 and CD133 were compared between the two experiments and showed differential expression patterns depending on the stage of carcinogensis and treatment with celecoxib. The flow cytometric analysis has shown that the numbers of CD133 were increased in the colonic epithelium after 12 weeks however, the numbers of CD44 but not CD133 cells were increased after 32 weeks. Moreover, the Aldehyde dehydrogenase-1 activity levels in the colonic epithelium (a known CSC marker) detected by ELISA assay were found down-regulated after 12 weeks, but were up-regulated after 32 weeks. The data have also shown that the protective effect of celecoxib on these specific markers and populations of CSCs and on other molecular processes such as the mRNA expression levels of APC and COX- genes and apoptosis targeted by this drug may vary depending on the genetic and phenotypic stages of carcinogenesis. Therefore,uncovering and correlating these distinctive roles of CSCs during different phases of carcinogenesis and during specific treatment could be useful for its targeted therapy