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1.  Anti-tumor effect of 5-aza-2'-deoxycytidine by inhibiting telomerase activity in hepatocellular carcinoma cells 
AIM: To investigate the effect of the demethylating reagent 5-aza-2’-deoxycitidine (DAC) on telomerase activity in hepatocellular carcinoma (HCC) cell lines, SMMC-7721 and HepG2.
METHODS: The related gene expression in cell lines was examined by real-time reverse transcription-polymerase chain reaction and Western blotting analysis. The telomerase activity was examined by telomeric repeat amplification protocol-enzyme-linked immunosorbent assay and DNA methylation was determined by methylation-specific polymerase chain reaction.
RESULTS: The telomerase activity was significantly reduced in both cell lines treated with DAC, accompanied by downregulation of telomerase reverse transcriptase (hTERT). We also observed the effect of DAC on the methylation status of hTERT promoter and the expression of regulatory genes, such as c-myc, p15, p16, p21, E2F1, and WT1. The methylation status of hTERT promoter could be reversed in SMMC-7721 by DAC, but not in HepG2 cells. However, p16 expression could be reactivated by demethylation of its promoter, and c-Myc expression was repressed in both cell lines. Moreover, DAC could enhance the sensitivity to the chemotherapeutic agents, such as cisplatin, by induction of apoptosis of HCC cells.
CONCLUSION: The DAC exerts its anti-tumor effects in HCC cells by inhibiting the telomerase activity.
doi:10.3748/wjg.v18.i19.2334
PMCID: PMC3353367  PMID: 22654424
5-aza-2’-deoxycitidine; Telomerase; Hepatocellular carcinoma; DNA methylation
2.  CD133+CXCR4+ colon cancer cells exhibit metastatic potential and predict poor prognosis of patients 
BMC Medicine  2012;10:85.
Background
Colorectal cancer (CRC), which frequently metastasizes to the liver, is one of the three leading causes of cancer-related deaths worldwide. Growing evidence suggests that a subset of cells exists among cancer stem cells. This distinct subpopulation is thought to contribute to liver metastasis; however, it has not been fully explored in CRC yet.
Methods
Flow cytometry analysis was performed to detect distinct subsets with CD133 and CXCR4 markers in human primary and metastatic CRC tissues. The 'stemness' and metastatic capacities of different subpopulations derived from the colon cancer cell line HCT116 were compared in vitro and in vivo. The roles of epithelial-mesenchymal transition (EMT) and stromal-cell derived factor-1 (SDF-1) in the metastatic process were also investigated. A survival curve was used to explore the correlation between the content of CD133+CXCR4+ cancer cells and patient survival.
Results
In human specimens, the content of CD133+CXCR4+ cells was higher in liver metastases than in primary colorectal tumors. Clonogenic and tumorigenic cells were restricted to CD133+ cells in the HCT116 cell line, with CXCR4 expression having no impact on the 'stemness' properties. We found that CD133+CXCR4+ cancer cells had a high metastatic capacity in vitro and in vivo. Compared with CD133+CXCR4- cells, CD133+CXCR4+ cancer cells experienced EMT, which contributed partly to their metastatic phenotype. We then determined that SDF-1/CXCL12 treatment could further induce EMT in CD133+CXCR4+ cancer cells and enhance their invasive behavior, while this could not be observed in CD133+CXCR4- cancer cells. Blocking SDF-1/CXCR4 interaction with a CXCR4 antagonist, AMD3100 (1,10-[1,4-phenylenebis(methylene)]bis-1,4,8,11 -tetraazacyclotetradecane octahydrochloride), inhibited metastatic tumor growth in a mouse hepatic metastasis model. Finally, a high percentage of CD133+CXCR4+ cells in human primary CRC was associated with a reduced two-year survival rate.
Conclusions
Strategies targeting the SDF-1/CXCR4 interaction may have important clinical applications in the suppression of colon cancer metastasis. Further investigations on how high expression of CXCR4 and EMT occur in this identified cancer stem cell subset are warranted to provide insights into our understanding of tumor biology.
doi:10.1186/1741-7015-10-85
PMCID: PMC3424958  PMID: 22871210
colorectal cancer; cancer stem cell; CXCR4; epithelial-mesenchymal transition; liver metastasis

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