title: Synergistic inhibitory effect of hyperbaric oxygen combined with sorafenib on hepatoma cells.
abstract: OBJECTIVE
  Hypoxia is a common phenomenon in solid tumors, associated with chemotherapy and radiotherapy resistance, recurrence and metastasis. Hyperbaric oxygen (HBO) therapy can increase tissue oxygen pressure and content to prevent the resistance, recurrence and metastasis of cancer. Presently, Sorafenib is a first-line drug, targeted for hepatocellular carcinoma (HCC) but effective in only a small portion of patients and can induce hypoxia. The purpose of this study is to investigate the effect of HBO in combination with sorafenib on hepatoma cells.
  
  
  METHODS
  Hepatoma cell lines (BEL-7402 and SK-Hep1) were treated with HBO at 2 atmosphere absolute pressure for 80 min per day or combined with sorafenib or cisplatin. At different time points, cells were tested for cell growth, colony formation, apoptosis, cell cycle and migration. Finally, miRNA from the hepatoma cells was detected by microRNA array and validated by qRT-PCR.
  
  
  RESULTS
  Although HBO, sorafenib or cisplatin alone could inhibit growth of hepatoma cells, HBO combined with sorafenib or cisplatin resulted in much greater synergistic growth inhibition (cell proliferation and colony formation) in hepatoma cells. Similarly, the synergistic effect of HBO and sorafenib on induction of apoptosis was also observed in hepatoma cells. HBO induced G1 arrest in SK-Hep1 not in BEL-7402 cells, but enhanced cell cycle arrest induced by sorafenib in BEL-7402 treated cells. However, HBO had no obvious effect on the migration of hepatoma cells, and microRNA array analysis showed that hepatoma cells with HBO treatment had significantly different microRNA expression profiles from those with blank control.
  
  
  CONCLUSIONS
  We show for the first time that HBO combined with sorafenib results in synergistic growth inhibition and apoptosis in hepatoma cells, suggesting a potential application of HBO combined with sorafenib in HCC patients. Additionally, we also show that HBO significantly altered microRNA expression in hepatoma cells.
authors: State Key Laboratory of Oncology in South China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors: Hai-Shan
authors: HS
authors: Peng
authors: Hyperbaric Oxygen Therapy Center, Affiliated Guangzhou First People's Hospital of Guangzhou Medical University, Guangzhou, China.
authors: Ming-Bin
authors: MB
authors: Liao
authors: State Key Laboratory of Oncology in South China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors: Mei-Yin
authors: MY
authors: Zhang
authors: State Key Laboratory of Oncology in South China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors: Yin
authors: Y
authors: Xie
authors: Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors: Li
authors: L
authors: Xu
authors: Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors: Yao-Jun
authors: YJ
authors: Zhang
authors: Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, New Jersey, United States of America.
authors: X F Steven
authors: XF
authors: Zheng
authors: State Key Laboratory of Oncology in South China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors: Hui-Yun
authors: HY
authors: Wang
authors: Hyperbaric Oxygen Therapy Center, Affiliated Guangzhou First People's Hospital of Guangzhou Medical University, Guangzhou, China.
authors: Yi-Fei
authors: YF
authors: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004357:Drug Synergism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D006931:Hyperbaric Oxygenation; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D010671:Phenylurea Compounds / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D000077157:Sorafenib; D014410:Tumor Stem Cell Assay
chemical_list: D035683:MicroRNAs; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib; D002945:Cisplatin