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

Huang,Mingsheng; Wang,Long; Chen,Junwei; Bai,Mingjun; Zhou,Churen; Liu,Sujuan; Lin,Qu

doi:10.3892/ijo.2016.3421

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

Authors:
- Mingsheng Huang
- Long Wang
- Junwei Chen
- Mingjun Bai
- Churen Zhou
- Sujuan Liu
- Qu Lin
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Affiliations: Department of Radiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, P.R. China, Department of Interventional Radiology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510630, P.R. China, Department of Medical Oncology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, P.R. China
Published online on: March 4, 2016 https://doi.org/10.3892/ijo.2016.3421
Pages: 2144-2154
Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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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