TF may participate in both K-ras and p53 mutations involved in colorectal carcinogenesis and could be considered as a prognostic indicator for patients CRC.
CD133-positive cancer stem cells in colon cancer are resistant to conventional chemotherapy. The aim of the present study was to investigate the effect of celecoxib, a COX-2 inhibitor, on CD133 expression in HT29 and DLD1 cells. HT29 and DLD1 cells were treated with celecoxib using different concentrations and duration. CD133 expression was detected by flow cytometry, Western blotting, immunofluorescence, and quantitative real-time PCR. Wnt signaling pathway activity was measured by luciferase assay and gene expression changes were monitored using microarray analysis. HT29 cells showed significantly decreasing levels of CD133 expression with increasing concentrations of or duration of exposure to celecoxib. CD133 mRNA relative expression in HT29 and DLD1 cells also decreased with drug exposure. Furthermore, Wnt activation in HT29 and DLD1 cells decreased with celecoxib treatment. Gene expression microarray showed stemness genes, including Lgr5, Oct4, Prominin-1, Prominin-2, CXCR4, E2F8, CDK-2, were downregulated and differentiation genes, including CEACAM5, GDF, ADFP, ICAM1, were upregulated. Our results show that CD133 expression was downregulated by celecoxib through inhibition of the Wnt signaling pathway, which may be lead to cell differentiation.
The objective of this study was to identify proteins that are differentially expressed in the cystic wall tissues of ovarian endometriotic cysts, simple ovarian cysts, and in normal ovarian tissues. Specimens of ovarian endometriotic cyst wall tissue, simple ovarian cyst wall tissue, and normal ovarian tissue (six specimens per group) were collected from patients who received gynecologic surgery, respectively. Differentially expressed proteins related to the ovarian endometriotic cysts were screened by use of isobaric tags for relative and absolute quantitation (iTRAQ) combined with functional annotation and bioinformatics analyses. All differentially expressed proteins related to cysts were validated using immunohistochemistry methods in recurrent and nonrecurrent ovarian endometriotic cyst. A total of 359 proteins were identified as up-regulated in ovarian endometriotic cyst groups when compared with both the normal ovary and simple ovarian cyst groups. The levels of 27 proteins were >two-fold higher in the ovarian endometriotic cyst group than that in the other two groups. Of note, the five most significantly upregulated proteins were Charcot-Leyden Crystal Galectin (CLC), Defensin, alpha 1 (DEFA1), S100 calciumbinding protein A9 (S100A9), S100 calcium-binding protein A8 (S100A8), and Ferritin Light Chain (FTL). Immunohistochemistry results showed that the changes of S100A9 and S100A8 were consistent with the results shown by iTRAQ. However, no similarity of CLC, DEFA1, and FTL proteins was found between iTRAQ and immunohistochemistry. The ratio of patients with abnormally high S100A9 and S100A8 expression in the recurrent ovarian endometriotic cyst group was significantly higher than that in the non-recurrent group (P < 0.05). Our data identify differentially expressed proteins S100A9 and S100A8, and suggest they may serve as novel molecular markers to predict postoperative recurrence of an ovarian endometriotic cysts.
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