5-Fluorouracil upregulates the activity of Wnt signaling pathway in CD133-positive colon cancer stem-like cells.
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BACKGROUND AND OBJECTIVE: CD133-positive colon cancer stem like cells (CSLCs) are resistant to the conventional cytotoxic drug 5-fluorouracil (5-FU). Wnt signaling pathway plays important roles in colon cancer carcinogenesis and metastasis, and regulates the self-renewal capacity of CSLCs. In the present study, we explored the impact of 5-FU on Wnt signaling pathway of CD133-positive colon CSLCs, and the relation between Wnt signaling pathway and drug resistance of CD133-positive colon CSLCs. METHODS: Magnetic activation cell separation was used to collect CD133-positive cells from colon cancer cell line DLD1, which was transfected with luciferase reporter for Wnt signaling activity. The activity of Wnt signaling pathway was compared between CD133-positive and CD133-negative cells. After the treatment with 1 mug/mL of 5-FU, the cell proliferation rates of DLD1 cells, CD133-positive cells, and CD133-negative cells were compared. After the treatment with 1 mug/mL and 10 mug/mL of 5-FU for 48 h, Wnt activity was compared between CD133-positive and CD133-negative cells. The expression of CD133 and cell apoptosis of CD133-positive cells was detected after exposure to 50 ng/mL of dickkopf (DKK)-1, a Wnt pathway inhibitor. RESULTS: After the treatment with 5-FU, the cell proliferation rate of CD133-positive cells was higher than that of CD133-negative cells and the sensitivity of CD133-positive cells to 5-FU decreased. Wnt activity was higher in CD133-positive cells than in CD133-negative cells [(46.3 +/- 0.3)% vs. (33.9 +/- 2.7)%, P = 0.009]. After the treatment with 1 mug/mL and 10 mug/mL of 5-FU, Wnt activity of CD133-positive cells was (90.1 +/- 10.0)% (P = 0.012) and (52.9 +/- 2.5)% (P = 0.047), respectively, whereas that of CD133-negative cells was (35.5 +/- 3.3)% (P = 0.434) and (26.5 +/- 0.4)% (P = 0.046), respectively. CD133 expression in CD133-positive cells decreased from (87.2 +/- 5.3)% to (60.6 +/- 3.1)% (P = 0.022) after treatment with DKK-1, whereas the cell apoptosis rate increased from (11.8 +/- 0.2)% to (28.3 +/- 0.6)% (P = 0.013). CONCLUSIONS: Wnt activity is higher in CD133-positive DLD1 cells than in CD133-negative DLD1 cells. 5-FU can upregulate Wnt activity of CD133-positive colon CSLCs. Blocking Wnt activity may reverse drug sensitivity of CD133-positive cells to 5-FU. (+info)
Identification of differentially expressed genes related to radioresistance of human esophageal cancer cells.
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BACKGROUND AND OBJECTIVE: Radioresistant cells in esophageal cancer is one of the important reasons for the local failure of radiotherapy. In recent years, some researchers used gene chip technology to screen the differentially expressed genes between parental and radioresistant human esophageal cancer cells. But there were some problems in these studies, for example comparing cells at only one time interval, and genetic background not matching. In this study, we selected 3 different pairs of parental and radioresistant human esophageal cancer cells, and compared the gene expression profiles by cDNA microarray at 3 time intervals to identify and analyze the differentially expressed genes between parental and radioresistant human esophageal cancer cells. METHODS: We compared the gene expression profiles between parental cells (TE13, Seg-1, Kyse170) and radioresistant cells (TE13R, Seg-1R, Kyse170R) before, and at 8 h and 24 h after irradiation with a cDNA microarray consisting of 48 000 genes (Human Genome). We identified differentially expressed genes by Pathway and GO analyses, and verified the differentially expressed genes LEF1 and CTNNB1 by RT-PCR. RESULTS: A total of 460, 451, and 397 differentially expressed genes were found before, and at 8 h and 24 h after irradiation. After Pathway and GO analyses, 14 differentially expressed genes, participating in cell growth, apoptosis, cell cycle regulation, gene repair and signal transmission, were selected to further research. LEF1 and CTNNB1 were verified by RT-PCR, and the results were consistent with those of cDNA microarray. CONCLUSIONS: The WNT signal pathway may be an important pathway participating in the formation of radioresistance of esophageal cancer cells. LEF1 and CTNNB1 may be the important genes causing the esophageal cancer cell radioresistance. (+info)
Mammary stem cells and cancer: roles of Wnt signaling in plain view.
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Canonical WNT signaling enhances stem cell expression in the developing heart without a corresponding inhibition of cardiogenic differentiation.
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