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  • Title: Regulation of COX-2 expression and epithelial-to-mesenchymal transition by hypoxia-inducible factor-1α is associated with poor prognosis in hepatocellular carcinoma patients post TACE surgery.
    Author: Huang M, Wang L, Chen J, Bai M, Zhou C, Liu S, Lin Q.
    Journal: Int J Oncol; 2016 May; 48(5):2144-54. PubMed ID: 26984380.
    Abstract:
    Currently, it is not entirely clear whether hypoxia-inducible factor-1α (HIF-1α) is involved in the regulation of COX-2 expression and epithelial-to-mesenchymal transition (EMT), and whether these events affect the prognosis of hepatocellular carcinoma (HCC) patients treated with transcatheter arterial chemoembolization (TACE). In this report the relationship between HIF-1α and COX-2 protein expression, EMT in tumor specimens from HCC patients after TACE surgery and the clinical significance of HIF-1α and COX-2 expression were analyzed using statistical approaches. HepG2 cells treated with CoCl2 was employed as a hypoxia cell model in vitro to study hypoxia-induced HIF-1α, COX-2 expression, and EMT alteration. The results showed that HIF-1α and COX-2 protein expression increased in HCC tissues after TACE surgery. Moreover, there was positive correlation between upregulation of HIF-1α and COX-2. Elevated expression of HIF-1α increased both Snail and Vimentin protein expression, while it reduced E-cadherin protein expression. It was further verified that hypoxia enhanced protein expression of HIF-1α and COX-2 in HepG2 cells treated with CoCl2. Upregulation of HIF-1α and COX-2, together with EMT alteration resulted in increased migration and invasion of HepG2 cells under hypoxia. In conclusion, TACE surgery results in aggravated hypoxia status, leading to increased HIF-1α protein expression in HCC tissue. To adapt to hypoxic environment, HIF-1α stimulates COX-2 protein expression and promotes EMT process in hepatocellular cancer cells, which enhances HCC invasion and metastasis, and might contribute to poor prognosis in HCC patients post TACE treatment.
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