Synergistic Inhibitory Effect of Hyperbaric Oxygen Combined with Sorafenib on Hepatoma Cells

Abstract

ObjectivesHypoxia 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.MethodsHepatoma 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.ResultsAlthough 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.ConclusionsWe 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.

Hyperbaric Oxygen Reduces Production of Reactive Oxygen Species in Neutrophils from Polytraumatized Patients Yielding in the Inhibition of p38 MAP Kinase and Downstream Pathways

“…The antiapoptotic Mcl-1 protein plays a critical role in the regulation of neutrophil apoptosis whereby decrease in intracellular protein levels usually correlate with increased apoptosis rate [ 34 ]. Previous studies postulated that HBO therapy provokes apoptosis in different cell types [ 35 – 37 ]. As depicted in Fig 5 , stimulation of cells with PMA triggered a strong decrease in intracellular Mcl-1 protein levels already after 4 h. However, this finding is particularly interesting as PMA was also found to increase the activity of p38 and ERK, the last one promoting Mcl-1 stabilization [ 38 ].…”

Hyperbaric Oxygen Therapy in Liver Diseases

“…Thus, hyperbaric oxygen combined with radiotherapy or chemotherapy has been intensively investigated 46 . An in vitro study showed that HBOT, sorafenib or cisplatin alone all could inhibit HCC cell growth, yet HBOT combined with sorafenib or cisplatin led to much greater synergistic proliferative inhibition and apoptotic induction 49 , suggesting a potential adjuvant application of HBOT in HCC patients.…”

Effects of hyperbaric oxygen treatment on gastric cancer cell line SGC7901

“…Some previous studies suggest that HBO therapy may improve postoperative outcome and outcome of radiotherapy and chemotherapy, especially proving beneficial for the treatment of radiotherapy (4,5). A combinatorial approach using chemotherapeutic drugs with HBO may enhance sensitivity of tumor cells to chemotherapeutic agents (6,7) and the application of HBO in chemotherapy for malignant lymphoma, brain tumor, lung cancer, gastric cancer and breast cancer may increase chemotherapeutic efficacy while decreasing treatment related toxicity (8). However, HBO treatment alone may stimulate the proliferation of tumor tissues (9).…”