Hyperoxia retards growth and induces apoptosis, changes in vascular density and gene expression in transplanted gliomas in nude rats

Abstract

This study describes the biological effects of hyperoxic treatment on BT4C rat glioma xenografts in vivo with special reference to tumor growth, angiogenesis, apoptosis, general morphology and gene expression parameters. One group of tumor bearing animals was exposed to normobaric hyperoxia (1 bar, pO(2) = 1.0) and another group was exposed to hyperbaric hyperoxia (2 bar, pO(2) = 2.0), whereas animals housed under normal atmosphere (1 bar, pO(2) = 0.2) served as controls. All treatments were performed at day 1, 4 and 7 for 90 min. Treatment effects were determined by assessment of tumor growth, vascular morphology (immunostaining for von Willebrand factor), apoptosis by TUNEL staining and cell proliferation by Ki67 staining. Moreover, gene expression profiles were obtained and verified by real time quantitative PCR. Hyperoxic treatment caused a approximately 60% reduction in tumor growth compared to the control group after 9 days (p < 0.01). Light microscopy showed that the tumors exposed to hyperoxia contained large "empty spaces" within the tumor mass. Moreover, hyperoxia induced a significant increase in the fraction of apoptotic cells ( approximately 21%), with no significant change in cell proliferation. After 2 bar treatment, the mean vascular density was reduced in the central parts of the tumors compared to the control and 1 bar group. The vessel diameters were significantly reduced (11-24%) in both parts of the tumor tissue. Evidence of induced cell death and reduced angiogenesis was reflected by gene expression analyses.Increased pO(2)-levels in experimental gliomas, using normobaric and moderate hyperbaric oxygen therapy, caused a significant reduction in tumor growth. This process is characterized by enhanced cell death, reduced vascular density and changes in gene expression corresponding to these effects.

Hyperbaric oxygen as a chemotherapy adjuvant in the treatment of osteosarcoma

“…More specifically, tumor cells are destroyed if ROS level rises beyond the limit of a tumor's resistance to oxidative stress following treatment with HBO. In fact, several recently published animal studies found that exposure to HBO alone induced tumor cell apoptosis (30)(31)(32). In the present study as well, DNA ladder formation was seen 48 h after treatment with HBO, while none was observed in the group without HBO treatment.…”

Effects of hyperbaric oxygen treatment on gastric cancer cell line SGC7901

“…However, the effect of hyperbaric oxygen treatment alone on tumor treatment remains controversial (21). Some studies suggested that HBO may possess tumor-inhibitory effects (22)(23)(24)(25), while others indicated that HBO treatment alone may stimulate tumor growth and metastasize (8,26,27).…”

Hyperbaric oxygen promotes malignant glioma cell growth and inhibits cell apoptosis

“…The increased density and morphological change of capillaries is associated with an increased degree of malignancy and a poorer prognosis (27,28). In the present study, the results demonstrated that increased MVD was associated with the proliferation of glioma cells, thus promoting angiogenesis; however, the opposite was observed in a subcutaneous model (18) and in breast cancer (29). The aforementioned observations indicate that the same intervention in different microenvironments may influence the growth of glioma cells differently (19).…”

“…transplanted glioma tumors (18). Due to the blood-brain barrier, numerous therapies that have proven effective for treating subcutaneous transplanted gliomas, may not be effective in treating intracranial primary gliomas (19).…”

“…Stuhr et al (18) proposed that hyperbaric oxygen may inhibit the growth of subcutaneous transplanted glioma cells in C57BL/6J mice; however, no cytological experiments were performed and the subcutaneous transplanted gliomas were quite different from intracranial gliomas, which originate from glia cells in situ (19).…”