The effect of hyperbaric oxygen treatment, alone or in combination with 5-FU, on a MDA-MB-231 human mammary tumor model

Background: Previous studies of hyperbaric oxygen (HBO) treatment on chemically induced and murine breast cancer models have shown promising results. This study was performed to elucidate the effects of HBO on a human breast cancer model, in an effort to make the results more clinically relevant. Our objective was to develop a human breast cancer model (MDA-MB-231) in NOD/SCID mice. This model was to be exposed to early or late hyperbaric oxygen therapy to evaluate effects concerning tumor growth, angiogenesis and proliferation. Finally, we wanted to elucidate if the effect of chemotherapy could be enhanced by HBO. Methods: Immunodeficient NOD/SCID mice were injected with the MDA-MB-231 cells to form tumors. Mice were divided in six groups: controls (early and late), HBO (early and late), chemotherapy (5FU) and HBO/5FU. Controls were exposed to normal ambient pressure air throughout the experiment, while HBO treatment was performed with pure oxygen 4 times (each 90 min) at 2.5 bar. 5FU was given immediately prior to HBO treatment in the combined group. Tumor growth was measured by a caliper. Immunostaining was used to discover differences in blood vessels (CD-31) and proliferating cells (KI-67). Results: The tumor model developed with 100 % take. Tumor growth was significantly inhibited in the early treated HBO group compared to controls, but not after late treatment. No differences were found in angiogenesis or proliferation between HBO and controls neither in the early nor the late group. Tumor size was not significantly different after the combined HBO/5FU treatment than after HBO alone. Conclusion: We can conclude that MDA-MB-231 tumor establishment was successful. HBO inhibits tumor growth significantly if given early, but not when administered late. This inhibitory effect could not be explained by differences in blood vessels or proliferating cell densities. HBO did not potentiate the effect of 5FU in this tumor model. Further studies are needed.