Hyperbaric oxygen promotes malignant glioma cell growth and inhibits cell apoptosis

Wang,Yong‑Gang; Zhan,Yi‑Ping; Pan,Shu‑Yi; Wang,Hai‑Dong; Zhang,Dun‑Xiao; Gao,Kai; Qi,Xue‑Ling; Yu,Chun‑Jiang

doi:10.3892/ol.2015.3244

Hyperbaric oxygen promotes malignant glioma cell growth and inhibits cell apoptosis

Authors:
- Yong‑Gang Wang
- Yi‑Ping Zhan
- Shu‑Yi Pan
- Hai‑Dong Wang
- Dun‑Xiao Zhang
- Kai Gao
- Xue‑Ling Qi
- Chun‑Jiang Yu
View Affiliations

Affiliations: Department of Neurosurgery, Beijing Sanbo Brain Hospital, Capital Medical University, Beijing 100093, P.R. China, Department of Hyperbaric Oxygen, Navy General Hospital, Beijing 100048, P.R. China, Institute of Laboratory Animal Sciences, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100021, P.R. China, Department of Pathology, Beijing Sanbo Brain Hospital, Capital Medical University, Beijing 100093, P.R. China
Published online on: May 20, 2015 https://doi.org/10.3892/ol.2015.3244
Pages: 189-195
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Glioblastoma multiforme (GBM) is the most frequently diagnosed intracranial malignant tumor in adults. Clinical studies have indicated that hyperbaric oxygen may improve the prognosis and reduce complications in glioma patients; however, the specific mechanism by which this occurs remains unknown. The present study investigated the direct effects of hyperbaric oxygen stimulation on glioma by constructing an intracranial transplanted glioma model in congenic C57BL/6J mice. Bioluminescent imaging (BLI) was used to assess the growth of intracranial transplanted GL261‑Luc glioma cells in vivo, while flow cytometric and immunohistochemical assays were used to detect and compare the expression of the biomarkers, Ki‑67, CD34 and TUNEL, reflecting the cell cycle, apoptosis and angiogenesis. BLI demonstrated that hyperbaric oxygen promoted the growth of intracranially transplanted GL261‑Luc glioma cells in vivo. Flow cytometric analysis indicated that hyperbaric oxygen promoted GL261‑Luc glioma cell proliferation and also prevented cell cycle arrest. In addition, hyperbaric oxygen inhibited the apoptosis of the transplanted glioma cells. Immunohistochemical analysis also indicated that hyperbaric oxygen increased positive staining for Ki‑67 and CD34, while reducing staining for TUNEL (a marker of apoptosis). The microvessel density was significantly increased in the hyperbaric oxygen treatment group compared with the control group. In conclusion, hyperbaric oxygen treatment promoted the growth of transplanted malignant glioma cells in vivo and also inhibited the apoptosis of these cells.

View Figures

View References

1	Stupp R, Mason WP, van den Bent MJ, et al European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 352:987–996. 2005. View Article : Google Scholar : PubMed/NCBI
2	Johnson DR and O'Neill BP: Glioblastoma survival in the United States before and during the temozolomide era. J Neurooncol. 107:359–364. 2012. View Article : Google Scholar : PubMed/NCBI
3	Sayegh ET, Kaur G, Bloch O and Parsa AT: Systematic review of protein biomarkers of invasive behavior in glioblastoma. Mol Neurobiol. 49:1212–1244. 2014. View Article : Google Scholar : PubMed/NCBI
4	Chamberlain MC: Neuro-oncology: A selected review of ASCO 2014 abstracts. CNS Oncology. 3:321–325. 2014. View Article : Google Scholar
5	Sathornsumetee S, Cao Y, Marcello JE, et al: Tumor angiogenic and hypoxic profiles predict radiographic response and survival in malignant astrocytoma patients treated with bevacizumab and irinotecan. J Clin Oncol. 26:271–278. 2008. View Article : Google Scholar : PubMed/NCBI
6	Jensen RL: Brain tumor hypoxia: Tumorigenesis, angiogenesis, imaging, pseudoprogression, and as a therapeutic target. J Neurooncol. 92:317–335. 2009. View Article : Google Scholar : PubMed/NCBI
7	Zhou Y, Zhou Y, Shingu T, et al: Metabolic alterations in highly tumorigenic glioblastoma cells: Preference for hypoxia and high dependency on glycolysis. J Biol Chem. 286:32843–32853. 2011. View Article : Google Scholar : PubMed/NCBI
8	Bar EE: Glioblastoma, cancer stem cells and hypoxia. Brain Pathol. 21:119–129. 2011. View Article : Google Scholar : PubMed/NCBI
9	Persano L, Rampazzo E, Della Puppa A, Pistollato F and Basso G: The three-layer concentric model of glioblastoma: Cancer stem cells, microenvironmental regulation, and therapeutic implications. ScientificWorldJournal. 11:1829–1841. 2011. View Article : Google Scholar : PubMed/NCBI
10	Brizel DM, Lin S, Johnson JL, Brooks J, Dewhirst MW and Piantadosi CA: The mechanisms by which hyperbaric oxygen and carbogen improve tumour oxygenation. Br J Cancer. 72:1120–1124. 1995. View Article : Google Scholar : PubMed/NCBI
11	Beppu T, Kamada K, Yoshida Y, Arai H, Ogasawara K and Ogawa A: Change of oxygen pressure in glioblastoma tissue under various conditions. J Neurooncol. 58:47–52. 2002. View Article : Google Scholar : PubMed/NCBI
12	Beppu T, Kamada K, Nakamura R, et al: A phase II study of radiotherapy after hyperbaric oxygenation combined with interferon-β and nimustine hydrochloride to treat supratentorial malignant gliomas. J Neurooncol. 61:161–170. 2003. View Article : Google Scholar : PubMed/NCBI
13	Kohshi K, Kinoshita Y, Imada H, et al: Effects of radiotherapy after hyperbaric oxygenation on malignant gliomas. Br J Cancer. 80:236–241. 1999. View Article : Google Scholar : PubMed/NCBI
14	Ogawa K, Ishiuchi S, Inoue O, et al: Phase II trial of radiotherapy after hyperbaric oxygenation with multiagent chemotherapy (procarbazine, nimustine, and vincristine) for high-grade gliomas: Long-term results. Int J Radiat Oncol Biol Phys. 82:732–738. 2012. View Article : Google Scholar : PubMed/NCBI
15	Kohshi K, Yamamoto H, Nakahara A, Katoh T and Takagi M: Fractionated stereotactic radiotherapy using gamma unit after hyperbaric oxygenation on recurrent high-grade gliomas. J Neurooncol. 82:297–303. 2007. View Article : Google Scholar : PubMed/NCBI
16	Sun S, Lee D, Lee NP, et al: Hyperoxia resensitizes chemoresistant human glioblastoma cells to temozolomide. J Neurooncol. 109:467–475. 2012. View Article : Google Scholar : PubMed/NCBI
17	Lu XY, Cao K, Li QY, Yuan ZC and Lu PS: The synergistic therapeutic effect of temozolomide and hyperbaric oxygen on glioma U251 cell lines is accompanied by alterations in vascular endothelial growth factor and multidrug resistance-associated protein-1 levels. J Int Med Res. 40:995–1004. 2012. View Article : Google Scholar : PubMed/NCBI
18	Stuhr LE, Raa A, Oyan AM, et al: Hyperoxia retards growth and induces apoptosis, changes in vascular density and gene expression in transplanted gliomas in nude rats. J Neurooncol. 85:191–202. 2007. View Article : Google Scholar : PubMed/NCBI
19	Biollaz G, Bernasconi L, Cretton C, et al: Site-specific anti-tumor immunity: Differences in DC function, TGF-β production and numbers of intratumoral Foxp3+ Treg. Eur J Immunol. 39:1323–1333. 2009. View Article : Google Scholar : PubMed/NCBI
20	Conconi MT, Baiguera S, Guidolin D, et al: Effects of hyperbaric oxygen on proliferative and apoptotic activities and reactive oxygen species generation in mouse fibroblast 3T3/J2 cell line. J Investig Med. 51:227–232. 2003. View Article : Google Scholar : PubMed/NCBI
21	Milovanova TN, Bhopale VM, Sorokina EM, et al: Hyperbaric oxygen stimulates vasculogenic stem cell growth and differentiation in vivo. J Appl Physiol. (1985)106:711–728. 2009.PubMed/NCBI
22	Kohshi K, Kinoshita Y, Terashima H, Konda N, Yokota A and Soejima T: Radiotherapy after hyperbaric oxygenation for malignant gliomas: A pilot study. J Cancer Res Clin Oncol. 122:676–678. 1996. View Article : Google Scholar : PubMed/NCBI
23	Maes W, Deroose C, Reumers V, et al: In vivo bioluminescence imaging in an experimental mouse model for dendritic cell based immunotherapy against malignant glioma. J Neurooncol. 91:127–139. 2009. View Article : Google Scholar : PubMed/NCBI
24	Stafford P, Abdelwahab MG, Kim Y, Preul MC, Rho JM and Scheck AC: The ketogenic diet reverses gene expression patterns and reduces reactive oxygen species levels when used as an adjuvant therapy for glioma. Nutr Metab (Lond). 7:74. 2010. View Article : Google Scholar : PubMed/NCBI
25	Calabrese C, Poppleton H, Kocak M, et al: A perivascular niche for brain tumor stem cells. Cancer Cell. 11:69–82. 2007. View Article : Google Scholar : PubMed/NCBI
26	Zagzag D, Amirnovin R, Greco MA, et al: Vascular apoptosis and involution in gliomas precede neovascularization: A novel concept for glioma growth and angiogenesis. Lab Invest. 80:837–849. 2000. View Article : Google Scholar : PubMed/NCBI
27	Deb P, Boruah D and Dutta V: Morphometric study of microvessels in primary CNS tumors and its correlation with tumor types and grade. Microvasc Res. 84:34–43. 2012. View Article : Google Scholar : PubMed/NCBI
28	Leon SP, Folkerth RD and Black PM: Microvessel density is a prognostic indicator for patients with astroglial brain tumors. Cancer. 77:362–372. 1996. View Article : Google Scholar : PubMed/NCBI
29	Moen I, Jevne C, Wang J, et al: Gene expression in tumor cells and stroma in dsRed 4T1 tumors in eGFP-expressing mice with and without enhanced oxygenation. BMC Cancer. 12:21. 2012. View Article : Google Scholar : PubMed/NCBI
30	Preusser M, Heinzl H, Gelpi E, et al European Organization for Research and Treatment of Cancer Brain Tumor Group: Histopathologic assessment of hot-spot microvessel density and vascular patterns in glioblastoma: Poor observer agreement limits clinical utility as prognostic factors: A translational research project of the European Organization for Research and Treatment of Cancer Brain Tumor Group. Cancer. 107:162–170. 2006. View Article : Google Scholar : PubMed/NCBI