A study on the expression of HIF-1α and COX-2 in rat&amp;apos;s radiation-induced oral mucositis

doi:10.3877/cma.j.issn.1674-1366.2008.03.003

Abstract

Abstract:

Objective

To investigate the mRNA and protein expressions of HIF-1 alpha and COX-2 in the rat tissues with radiation induced mucositis （ROM）， and to analyze the correlation between the expression level of HIF-1 alpha and COX-2.

Methods

The rat model with ROM was established. The left buccal mucosa was excised as experimental tissue， whereas the right buccal mucosa was excised to serve as control tissue. The relative mRNA expressions of HIF-1 alpha and COX-2 were measured using the semi quantitative RT-PCR. The immunohistochemistry of Strept Avidin-Biotin-Complex Method （SABC Method） was employed to detect the distribution and intensity of HIF-1 alpha and COX-2 proteins.

Results

We successfully established a Sprague-Dawley rat model of ROM. The results of RT-PCR indicated that the left buccal mucosa expressed HIF-1 alpha and COX-2 mRNAs， while the right buccal mucosa showed negative expression of both genes. Immunohistochemical analysis demonstrated simultaneous expressions of HIF-1 alpha and COX-2 proteins in the left side mucosa.

Conclusions

The mucosa of ROM expresses HIF-1 alpha and COX-2 at mRNA and protein levels， which is correlated with the severity of ROM. A high correlation between HIF-1 alpha and COX-2 expressions has also been confirmed in this study.

Key words: Hypoxia inducible factor-1α, Cyclooxygenase-2, Radiation, Oral mucositis

Jun-bing GUO, Shuang-xi ZHU, Chi-bin LI, Chun-yang LI, Bin CHENG, Hong-wei JIANG, Yong CHEN, Han-yu WANG, Chong-jin FENG. A study on the expression of HIF-1α and COX-2 in rat's radiation-induced oral mucositis[J]. Chinese Journal of Stomatological Research(Electronic Edition), 2008, 02(03): 217-227.

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URL: https://zhkqyxyjzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-1366.2008.03.003

https://zhkqyxyjzz.cma-cmc.com.cn/EN/Y2008/V02/I03/217

Figures/Tables 9

References 19

1	Trotti A， Bellm LA， Epstein JB， et al. Mucositis incidence， severity and associated outcomes in patients with head and neck cancer receiving radiotherapy with or without chemotherapy： a systematic literature review. Radiother Oncol， 2003，66（3）：253-262.
2	Sonis ST， Peterson RL， Edwards LJ， et al. Defining mechanisms of action of interleukin-11 on the progression of radiation-induced oral mucositis in hamsters. Oral Oncol， 2000，36（4）：373-381.
3	Koga H， Sakisaka S， Ohishi M， et al. Expression of cyclooxygenase-2 in human hepatocellular carcinoma： relevance to tumor dedifferentiation. Hepatology， 1999，29（3）：688-696.
4	Bloomer WD， Hellman S. Normal tissue responses to radiation therapy. N Engl J Med， 1975，293（2）：80-83.
5	Sonis ST， Elting LS， Keefe D， et al. Perspectives on cancer therapy-induced mucosal injury： pathogenesis， measurement， epidemiology，and consequences for patients. Cancer， 2004，100 （9 Suppl）：1995-2025.
6	Sonis ST. The pathobiology of mucositis. Nat Rev Cancer， 2004，4（4）：277-284.
7	Semenza GL. Hypoxia-inducible factor 1： control of oxygen homeostasis in health and disease. Pediatr Res， 2001，49（5）：614-617.
8	McNeill LA， Hewitson KS， Gleadle JM， et al. The use of dioxygen by HIF prolyl hydroxylase （PHD1）. Bioorg Med Chem Lett， 2002，12（12）：1547-1550.
9	Metzen E， Zhou J， Jelkmann W， et al. Nitric oxide impairs normoxic degradation of HIF-1alpha by inhibition of prolyl hydroxylases. Mol Biol Cell， 2003，14（8）：3470-3481.
10	Thornton RD， Lane P， Borghaei RC， et al. Interleukin 1 induces hypoxia-inducible factor 1 in human gingival and synovial fibroblasts.Biochem J， 2000，350（Pt 1）：307-312.
11	Albina JE， Mastrofrancesco B， Vessella JA， et al. HIF-1 expression in healing wounds： HIF-1alpha induction in primary inflammatory cells by TNF-alpha. Am J Physiol Cell Physiol， 2001，281（6）：C1971-1977.
12	Sonis ST. The biologic role for nuclear factor-kappaB in disease and its potential involvement in mucosal injury associated with anti-neoplastic therapy. Crit Rev Oral Biol Med， 2002，13（5）： 380-389.
13	Haddad JJ， Land SC. A non-hypoxic， ROS-sensitive pathway mediates TNF-alpha-dependent regulation of HIF-1alpha. FEBS Lett，2001，505（2）：269-274.
14	Jung YJ， Isaacs JS， Lee S， et al. IL-1beta-mediated up-regulation of HIF-1alpha via an NFkappaB/COX-2 pathway identifies HIF-1 as a critical link between inflammation and oncogenesis. FASEB J， 2003，17（14）：2115-2117.
15	Jeong HJ， Chung HS， Lee BR， et al. Expression of proinflammatory cytokines via HIF-1alpha and NF-kappaB activation on desferrioxamine-stimulated HMC-1 cells. Biochem Biophys Res Commun， 2003，306（4）：805-811.
16	Carey MA， Bradbury JA， Seubert JM， et al. Contrasting effects of cyclooxygenase-1（COX-1） and COX-2 deficiency on the host response to influenza A viral infection. J Immunol， 2005，175（10）：6878-6884.
17	Kurumbail RG， Stevens AM， Gierse JK， et al. Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents.Nature， 1996，384（6610）：644-648.
18	Lukiw WJ， Ottlecz A， Lambrou G， et al. Coordinate activation of HIF-1 and NF-kappaB DNA binding and COX-2 and VEGF expression in retinal cells by hypoxia. Invest Ophthalmol Vis Sci， 2003，44（10）：4163-4170.
19	夏若寒，郝天玲，于江洲，等. 缺氧诱导因子-1 和红细胞生成素3′-增强子调节内皮细胞环氧合酶和血栓素合酶基因转录. 中国应用生理学杂志， 2000，16（1）：48-51.

组别	标本数	左侧颊黏膜	右侧颊黏膜
20 Gy	6	0.48±0.07	0.20±0.02
40 Gy	6	0.53±0.06	0.23±0.04
60 Gy	6	0.68±0.08	0.46±0.04
80 Gy	6	0.75±0.08	0.31±0.05
2 d	6	0.77±0.06	0.33±0.05
4 d	6	0.87±0.06	0.26±0.02
6 d	6	0.81±0.08	0.25±0.06
8 d	6	0.32±0.04	0.21±0.03
14 d^*	6	0.26±0.07	0.22±0.03
21 d^*	6	0.12±0.02	0.11±0.02

组别	标本数	左侧颊黏膜	右侧颊黏膜
20 Gy	6	0.48±0.07	0.20±0.02
40 Gy	6	0.53±0.06	0.23±0.04
60 Gy	6	0.68±0.08	0.46±0.04
80 Gy	6	0.75±0.08	0.31±0.05
2 d	6	0.77±0.06	0.33±0.05
4 d	6	0.87±0.06	0.26±0.02
6 d	6	0.81±0.08	0.25±0.06
8 d	6	0.32±0.04	0.21±0.03
14 d^*	6	0.26±0.07	0.22±0.03
21 d^*	6	0.12±0.02	0.11±0.02

组别	标本数	左侧	右侧
20 Gy	6	0.40±0.06	0.20±0.03
40 Gy	6	0.48±0.07	0.23±0.03
60 Gy	6	0.61±0.08	0.29±0.05
80 Gy	6	0.74±0.06	0.28±0.03
2 d	6	0.77±0.06	0.30±0.07
4 d	6	0.90±0.06	0.16±0.04
6 d	6	0.87±0.04	0.15±0.08
8 d^*	6	0.26±0.05	0.25±0.07
14 d^*	6	0.27±0.05	0.21±0.05
21 d^*	6	0.10±0.02	0.09±0.01

组别	标本数	左侧	右侧
20 Gy	6	0.40±0.06	0.20±0.03
40 Gy	6	0.48±0.07	0.23±0.03
60 Gy	6	0.61±0.08	0.29±0.05
80 Gy	6	0.74±0.06	0.28±0.03
2 d	6	0.77±0.06	0.30±0.07
4 d	6	0.90±0.06	0.16±0.04
6 d	6	0.87±0.04	0.15±0.08
8 d^*	6	0.26±0.05	0.25±0.07
14 d^*	6	0.27±0.05	0.21±0.05
21 d^*	6	0.10±0.02	0.09±0.01

组别	标本数	HIF-1α（%）	COX-2（%）
control	6	2.07±0.39	1.59±0.28
20 Gy	6	4.73±0.60	4.63±0.54
40 Gy	6	20.36±5.95	13.84±4.43
60 Gy	6	41.85±5.47	41.48±4.44
80 Gy	6	60.75±7.02	52.72±3.71
2 d	6	64.45±4.74	72.08±6.98
4 d	6	81.42±5.91	68.80±6.08
6 d	6	61.70±3.50	53.63±5.38
8 d	6	33.65±7.93	29.75±10.67
14 d	6	5.63±0.95	4.81±1.24
21 d	6	3.24±0.64	3.34±0.79

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A study on the expression of HIF-1α and COX-2 in rat's radiation-induced oral mucositis