In colorectal cancer, no study has been carried out discovering the relationship among p53, mitochondrial transcription factor A (TFAM) expression and change of mitochondrial DNA (mtDNA) copy number. In our study, co-expression of p53 and TFAM was observed in colon adenocarcinoma tissues, paracancerous tissues and 9 colorectal cancer cell lines. Then, a significant linear correlation was established between either p53 or TFAM expression and advanced TNM stage, positive lymph nodes and low 5-year survival rate in patients with colon adenocarcinoma. Additionally, advanced TNM stage, large tumor burden, presence of distant metastasis, and high TFAM expression were significantly related to poor overall 5-years survival. Moreover, alteration of p53 expression could change TFAM expression but TFAM could not influence p53 expression, and p53 could enhance TFAM expression via binding to TFAM promoter. While, both of p53 and TFAM expression could incrase mtDNA copy number in vitro. In conclusions, p53 might incrase mtDNA copy number through its regulation on TFAM expression via TFAMpromoter.
Purpose:
Biomarkers are lacking in hepatocellular carcinoma (HCC). Cyclooxygenase-2 (COX-2) and its metabolites play crucial roles in the process of inflammation-tumor transformation. This study was aimed to detect COX-2 expression in HCC tissues and evaluate the effects of a COX-2 inhibitor, celecoxib, on biological behaviors of HCC cell lines in vitro.
Methods:
COX-2 expression was detected by immunohistochemistry on a human HCC tissue microarray. The correlations of COX-2 expression with tumor clinicopathological variables and overall survival were analyzed. The proliferation, apoptosis, cell cycle distribution, invasion capacity, and related signaling molecules of HCC cells after incubated with COX-2 inhibitor celecoxib were evaluated in vitro.
Results:
Expression levels of COX-2 in HCC tissues were significantly higher than those in paracancerous tissues. The TNM stage III-IV, tumor size >5 cm, lymphovascular invasion and distant metastasis was higher in high COX-2 expression group compared with that in low COX-2 expression group. Patients with low COX-2 expression achieved better 5-year overall survival than those with high COX-2 expression. Treatment with celecoxib was sufficient to inhibit cell proliferation, promote apoptosis, and induce G0/G1 cell cycle arrest in HCC cells with concentration- and time-dependent manners. Celecoxib up-regulated E-cadherin protein through inhibiting COX-2-prostaglandin E2 (PGE2)-PGE2 receptor 2 (EP2)-p-Akt/p-ERK signaling pathway to suppress HCC cells migration and invasion.
Conclusion:
High COX-2 expression was associated with advanced TNM stage, larger tumor size, increased lymphovascular invasion and short survival. Targeting inhibition of COX-2 by celecoxib exhibited anti-tumor activities by suppressing proliferation, promoting apoptosis, and inhibiting the aggressive properties of HCC cells.
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