Browse > Article
http://dx.doi.org/10.3857/jkstro.2009.27.4.218

Different Expressions of HIF-$1\alpha$, Bcl-2 and Baxin DU145 Prostate Cancer Cells Transplanted in Nude Mouse between X-Ray and Neutron Irradiation  

Kong, Moon-Kyoo (Departments of Radiation Oncology, Kyung Hee University School of Medicine)
Kang, Jin-Oh (Departments of Radiation Oncology, Kyung Hee University School of Medicine)
Kim, Sang-Ki (Departments of Radiation Oncology, Kyung Hee University School of Medicine)
Shin, Dong-Oh (Departments of Radiation Oncology, Kyung Hee University School of Medicine)
Park, Seo-Hyun (Departments of Radiation Oncology, Kyung Hee University School of Medicine)
Kim, Chang-Ju (Departments of Physiology, Kyung Hee University School of Medicine)
Chang, Hyun-Kyung (Departments of Physiology, Kyung Hee University School of Medicine)
Publication Information
Radiation Oncology Journal / v.27, no.4, 2009 , pp. 218-227 More about this Journal
Abstract
Purpose: To investigate the radiobiologic effects of neutron and X-ray irradiation on DU-145 prostate carcinoma cells by identifying the differences of HIF-$1\alpha$ expression and apoptosis. Materials and Methods: Nude mice were injected with the human prostate cancer cell line, DU-145, and then irradiated with 2 Gy and 10 Gy X-rays, or 0.6 Gy and 3.3 Gy neutrons, respectively. The mice were sacrificed at 24 hours and 120 hours after irradiation. The expression levels of HIF-$1\alpha$, Bcl-2 and Bax were compared with immunohistochemical staining and western blotting. The apoptotic indexes were compared with the Terminal deoxynucleotidyl biotin-dUTP nick and labeling (TUNEL) assay. Results: At day 1, HIF-$1\alpha$ and Bcl-2 expression decreased, while Bax expression and the number of TUNEL positive cells increased in neutron irradiated groups for the control and X-ray irradiated groups. The Bcl-2/Bax ratio was significantly lower in the neutron irradiated groups regardless of dose (p=0.001). The same pattern of the differences in the expressions of the HIF-$1\alpha$, Bcl-2, Bax, Bcl-2/Bax ratio, and apoptotic indexes were indentified at day 5. HIF-$1\alpha$ expression was related with Bcl-2 (p=0.031), Bax (p=0.037) expressions and the apoptotic indexes (p=0.016) at day 5. Conclusion: Neutron irradiation showed a decrease in HIF-$1\alpha$, Bcl-2 expression, and Bcl-2/Bax ratio, but increased Bax expression regardless of dose. This study suggests that the differences radiobiological responses between photon and neutron irradiation may be related to different HIF-$1\alpha$ expression and subsequent apoptotic protein expressions.
Keywords
HIF-$1\alpha$; Bcl-2; Bax; Neutron; Prostate cancer;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Halperin EC. Particle therapy and treatment of cancer. Lancet Oncol 2006;7:676-685   DOI   PUBMED   ScienceOn
2 Vral A, Cornelissen M, Thierens H, et al. Apoptosis induced by fast neutrons versus 60Co gamma-rays in human peripheral blood lymphocytes. Int J Radiat Biol 1998;73:289-295   DOI   ScienceOn
3 Meijer AE, Kronqvist US, Lewensohn R, Harms-Ringdahl M. RBE for the induction of apoptosis in human peripheral lymphocytes exposed in vitro to high-LET radiation generated by accelerated nitrogen ions. Int J Radiat Biol 1998;73:169-177   DOI   ScienceOn
4 Kyprianou N, King ED, Bradbury D, Rhee JG. Bcl-2 over-expression delays radiation-induced apoptosis without affecting the clonogenic survival of human prostate cancer cells. Int J Cancer 1997;70:341-348   DOI   ScienceOn
5 Szostak MJ, Kaur P, Amin P, Jacobs SC, Kyprianou N. Apoptosis and bcl-2 expression in prostate cancer: significance in clinical outcome after brachytherapy. J Urol 2001;165:2126-2130   DOI   PUBMED   ScienceOn
6 Mu Z, Hachem P, Pollack A. Antisense Bcl-2 sensitizes prostate cancer cells to radiation. Prostate 2005;65:331-340   DOI   ScienceOn
7 Russell KJ, Caplan RJ, Laramore GE, et al. Photon versus fast neutron external beam radiotherapy in the treatment of locally advanced prostate cancer: results of a randomized prospective trial. Int J Radiat Oncol Biol Phys 1994;28:47-54   DOI   PUBMED   ScienceOn
8 Piret JP, Mottet D, Raes M, Michiels C. Is HIF-1alpha a pro- or an anti-apoptotic protein? Biochem Pharmacol 2002;64:889-892   DOI   PUBMED   ScienceOn
9 Eom KY, Wu HG, Park HJ, et al. Evaluation of biological characteristics of neutron beam generated from MC50 cyclotron. J Korean Soc Ther Radiol Oncol 2006;24:280-284
10 Lee HJ, Kim JS, Moon C, Kim JC, Jo SK, Kim SH. Relative biological effectiveness of fast neutrons in a multiorgan assay for apoptosis in mouse. Environ Toxicol 2008;23:233-239   DOI   ScienceOn
11 Strowbridge A, Wall N, Aref A, et al. Neutron radiation induces the modulation of BCL-2 and BAX protein resulting in apoptosis in a chemotherapy resistant intermediate grade non-Hodgkin's lymphoma cell line. Proc Am Soc Clin Oncol 2000;19:abstr 2601
12 Moeller BJ, Richardson RA, Dewhirst MW. Hypoxia and radiotherapy: opportunities for improved outcomes in cancer treatment. Cancer Metastasis Rev 2007;26:241-248   DOI   ScienceOn
13 Mackey TJ, Borkowski A, Amin P, Jacobs SC, Kyprianou N. bcl-2/bax ratio as a predictive marker for therapeutic response to radiotherapy in patients with prostate cancer. Urology 1998;52:1085-1090   DOI   PUBMED   ScienceOn
14 Holl V, Coelho D, Weltin D, Dufour P, Gueulette J, Bischoff P. Ex vivo determination of the effect of whole-body exposure to fast neutrons on murine spleen cell viability and apoptosis. Radiat Res 2000;154:301-306   DOI   ScienceOn
15 Wang LP, Liang K, Shen Y, Yin WB, Hans G, Zeng YJ. Neutron-induced apoptosis of HR8348 cells in vitro. World J Gastroenterol 2001;7:435-439   DOI   PUBMED
16 Moeller BJ, Cao Y, Li CY, Dewhirst MW. Radiation activates HIF-1 to regulate vascular radiosensitivity in tumors:role of reoxygenation, free radicals, and stress granules. Cancer Cell 2004;5:429-441   DOI   ScienceOn
17 Wambersie A, Hendry J, Gueulette J, Gahbauer R, Potter R, Gregoire V. Radiobiological rationale and patient selection for high-LET radiation in cancer therapy. Radiother Oncol 2004;73 Suppl 2:S1-14
18 Zhong H, Semenza GL, Simons JW, De Marzo AM. Up-regulation of hypoxia-inducible factor 1alpha is an early event in prostate carcinogenesis. Cancer Detect Prev 2004;28:88-93   DOI   ScienceOn
19 Moeller BJ, Dreher MR, Rabbani ZN, et al. Pleiotropic effects of HIF-1 blockade on tumor radiosensitivity. Cancer Cell 2005;8:99-110   DOI   ScienceOn
20 Forman JD, Yudelev M, Bolton S, Tekyi-Mensah S, Maughan R. Fast neutron irradiation for prostate cancer. Cancer Metastasis Rev 2002;21:131-135   DOI   ScienceOn
21 Khor LY, Desilvio M, Li R, et al. Bcl-2 and bax expression and prostate cancer outcome in men treated with radiotherapy in Radiation Therapy Oncology Group protocol 86-10. Int J Radiat Oncol Biol Phys 2006;66:25-30   DOI   PUBMED   ScienceOn
22 Hall EJ, Giaccia AJ. Radiobiology for the radiologist. 6th ed. Philadelphia: Lippincott Williams & Wilkins, 2006:109
23 Anastasiadis AG, Stisser BC, Ghafar MA, Burchardt M, Buttyan R. Tumor hypoxia and the progression of prostate cancer. Curr Urol Rep 2002;3:222-228   DOI   ScienceOn
24 Chan N, Milosevic M, Bristow RG. Tumor hypoxia, DNA repair and prostate cancer progression: new targets and new therapies. Future Oncol 2007;3:329-341   DOI   ScienceOn
25 Semenza GL. Angiogenesis in ischemic and neoplastic disorders. Annu Rev Med 2003;54:17-28   DOI   PUBMED   ScienceOn
26 Khor LY, Moughan J, Al-Saleem T, et al. Bcl-2 and Bax expression predict prostate cancer outcome in men treated with androgen deprivation and radiotherapy on radiation therapy oncology group protocol 92-02. Clin Cancer Res 2007;13:3585-3590   DOI   ScienceOn