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.
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.
authors.affiliation: Department of Radiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, P.R. China.
authors.forename: Mingsheng
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Interventional Radiology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510630, P.R. China.
authors.forename: Long
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Radiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, P.R. China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Radiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, P.R. China.
authors.forename: Mingjun
authors.initials: M
authors.lastname: Bai
authors.affiliation: Department of Radiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, P.R. China.
authors.forename: Churen
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Radiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, P.R. China.
authors.forename: Sujuan
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, P.R. China.
authors.forename: Qu
authors.initials: Q
authors.lastname: Lin
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D015687:Cell Hypoxia; D002465:Cell Movement; D016461:Chemoembolization, Therapeutic / Q000009:adverse effects*; D003035:Cobalt / Q000009:adverse effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D003035:Cobalt; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C018021:cobaltous chloride