title: Dexamethasone inhibits hypoxia-induced epithelial-mesenchymal transition in colon cancer.
abstract: OBJECTIVE
  To elucidate the effects of dexamethasone on hypoxia-induced epithelial-to-mesenchymal transition (EMT) in colon cancer.
  
  
  METHODS
  Human colon cancer HCT116 and HT29 cells were exposed to normoxic (21%) and hypoxic (1%) conditions. First, the effect of dexamethasone on cell viability was examined by MTT cell proliferation assay. In order to measure the expression levels of EMT markers (Snail, Slug, Twist, E-cadherin, and integrin αVβ6) and hypoxia-related genes [Hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF)] by dexamethasone, quantitative real-time polymerase chain reaction and western blot analysis were performed. Furthermore, the morphological changes of colon cancer cells and the expression pattern of E-cadherin by dexamethasone were detected through immunocytochemistry. Finally, the effects of dexamethasone on the invasiveness and migration of colon cancer cells were elucidated using matrigel invasion, migration, and wound healing migration assays.
  
  
  RESULTS
  Under hypoxia, dexamethasone treatment inhibited HIF-1α protein level and its downstream gene, VEGF mRNA level in the colon cancer cell lines, HCT116 and HT29. In addition, the presence of dexamethasone down-regulated the mRNA levels of hypoxia-induced Snail, Slug, and Twist, all transcriptional factors of EMT, as well as hypoxia-induced integrin αVβ6 protein level, a well-known EMT marker for colon cancer cells. Furthermore, reduced E-cadherin in hypoxic condition was found to be recoverable by treating with dexamethasone in both colon cancer cell lines. Similarly, under hypoxic conditions, dexamethasone restored the growth pattern and morphological phenotype reminiscent of colon cancer cells grown under normoxic conditions; dexamethasone blocked the migration and invasion of both colorectal cancer cell lines in hypoxia.
  
  
  CONCLUSIONS
  Our study suggested that dexamethasone has inhibitory effects on cell migration and invasion by suppressing EMT of colon cancer cell lines in hypoxic condition.
authors.affiliation: Jung Ho Kim, Young Eun Lee, Saerom Kim, Yoon Jae Kim, Jae Hee Cho, Kwang An Kwon, Ju Hyun Kim, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 405-760, South Korea.
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Jung Ho Kim, Young Eun Lee, Saerom Kim, Yoon Jae Kim, Jae Hee Cho, Kwang An Kwon, Ju Hyun Kim, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 405-760, South Korea.
authors.forename: You-Jin
authors.initials: YJ
authors.lastname: Hwang
authors.affiliation: Jung Ho Kim, Young Eun Lee, Saerom Kim, Yoon Jae Kim, Jae Hee Cho, Kwang An Kwon, Ju Hyun Kim, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 405-760, South Korea.
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Han
authors.affiliation: Jung Ho Kim, Young Eun Lee, Saerom Kim, Yoon Jae Kim, Jae Hee Cho, Kwang An Kwon, Ju Hyun Kim, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 405-760, South Korea.
authors.forename: Young Eun
authors.initials: YE
authors.lastname: Lee
authors.affiliation: Jung Ho Kim, Young Eun Lee, Saerom Kim, Yoon Jae Kim, Jae Hee Cho, Kwang An Kwon, Ju Hyun Kim, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 405-760, South Korea.
authors.forename: Saerom
authors.initials: S
authors.lastname: Kim
authors.affiliation: Jung Ho Kim, Young Eun Lee, Saerom Kim, Yoon Jae Kim, Jae Hee Cho, Kwang An Kwon, Ju Hyun Kim, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 405-760, South Korea.
authors.forename: Yoon Jae
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Jung Ho Kim, Young Eun Lee, Saerom Kim, Yoon Jae Kim, Jae Hee Cho, Kwang An Kwon, Ju Hyun Kim, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 405-760, South Korea.
authors.forename: Jae Hee
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Jung Ho Kim, Young Eun Lee, Saerom Kim, Yoon Jae Kim, Jae Hee Cho, Kwang An Kwon, Ju Hyun Kim, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 405-760, South Korea.
authors.forename: Kwang An
authors.initials: KA
authors.lastname: Kwon
authors.affiliation: Jung Ho Kim, Young Eun Lee, Saerom Kim, Yoon Jae Kim, Jae Hee Cho, Kwang An Kwon, Ju Hyun Kim, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 405-760, South Korea.
authors.forename: Ju Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Jung Ho Kim, Young Eun Lee, Saerom Kim, Yoon Jae Kim, Jae Hee Cho, Kwang An Kwon, Ju Hyun Kim, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 405-760, South Korea.
authors.forename: Se-Hee
authors.initials: SH
authors.lastname: Kim
mesh_terms: D015703:Antigens, CD; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D015687:Cell Hypoxia; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D020128:Inhibitory Concentration 50; D009361:Neoplasm Invasiveness; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D059016:Tumor Microenvironment; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000970:Antineoplastic Agents; C513384:CDH1 protein, human; D015820:Cadherins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D003907:Dexamethasone
keywords: Colon cancer; Dexamethasone; Epithelial-mesenchymal transition; Hypoxia; Hypoxia-inducible factor-1α