过表达HIF-1α和VEGF蛋白与垂体腺瘤侵袭行为的关系
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摘要
目的:探讨缺氧诱导因子-1α(HIF-1α)和血管内皮生长因子(VEGF)在垂体腺瘤中的表达及与垂体腺瘤侵袭性的关系。方法:收集的32例垂体腺瘤标本中侵袭性垂体腺瘤20例,非侵袭性垂体腺瘤12例,应用免疫组化染色检测HIF-1α和VEGF蛋白的表达。并对侵袭组与非侵袭组的HIF-1α和VEGF蛋白表达及不同大小肿瘤HIF-1α和VEGF蛋白表达进行分析比较。结果:非侵袭组垂体腺瘤中HIF-1α和VEGF蛋白表达阳性率与侵袭组比较,差异有统计学意义(P<0.05);垂体腺瘤直径大于30 mm者HIF-1α和VEGF蛋白表达阳性率与直径10~30 mm者比较,差异有统计学意义(P<0.05)。结论:HIF-1α和VEGF蛋白在侵袭性垂体腺瘤中的表达明显增加,并且与垂体腺瘤侵袭行为密切相关。
Objective:To explore the protein expression of hypoxia-inducible fator-1α and VEGF in pituitary adenoma and their relation with invasion of pituitary adenoma. Methods:Among the collected data of 32 cases of pituitary adenoma,20 cases were invasive pituitary adenoma and 12 cases were non-invasive pituitary adenoma. Immunochemistry staining was used to determine the protein expression of HIF-1α and VEGF. Protein expression of invasive pituitary adenoma group and non-invasive pituitary adenoma group and the protein expression of HIF-1α and VEGF in pituitary adenomas with different size were analyzed and compared. Results:The positive rate of protein expression of HIF-1α and VEGF in invasive pituitary adenomas group showed statistically significant compared with that of the non-invasive pituitary adenomas group( P < 0. 05). The positive rate of protein expression of HIF-1αand VEGF in pituitary adenomas with diameter larger than thirty mm showed statistically significant compared with those with diameters between ten mm to thirty mm( P < 0. 05). Conclusion:There were overexpression of HIF-1αand VEGF in pituitary adenomas,and these studies that the activation of HIF-1α and VEGF protein can increase the invasion of pituitary adenomas.
Objective:To explore the protein expression of hypoxia-inducible fator-1α and VEGF in pituitary adenoma and their relation with invasion of pituitary adenoma. Methods:Among the collected data of 32 cases of pituitary adenoma,20 cases were invasive pituitary adenoma and 12 cases were non-invasive pituitary adenoma. Immunochemistry staining was used to determine the protein expression of HIF-1α and VEGF. Protein expression of invasive pituitary adenoma group and non-invasive pituitary adenoma group and the protein expression of HIF-1α and VEGF in pituitary adenomas with different size were analyzed and compared. Results:The positive rate of protein expression of HIF-1α and VEGF in invasive pituitary adenomas group showed statistically significant compared with that of the non-invasive pituitary adenomas group( P < 0. 05). The positive rate of protein expression of HIF-1αand VEGF in pituitary adenomas with diameter larger than thirty mm showed statistically significant compared with those with diameters between ten mm to thirty mm( P < 0. 05). Conclusion:There were overexpression of HIF-1αand VEGF in pituitary adenomas,and these studies that the activation of HIF-1α and VEGF protein can increase the invasion of pituitary adenomas.
引文
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[12]Kun Z,Yuling Y,Dongchun W,et al.HIF-1αinhibition sensitized pituitary adenoma cells to temozolomide by regulating presenilin 1 expression and autophagy[J].Technol Cancer Res Treat,2016,15(6):95-104.
[13]Chen W,Xiao Z,Zhao Y,et al.HIF-1αinhibition sensitizes pituitary adenoma cells to temozolomide by regulating MGMT expression[J].Oncol Rep,2013,30(5):2495-2501.
[14]Wu J,Ke X,Ma N,et al.Formononetin,an active compound of astragalus membranaceus(Fisch)Bunge,inhibits hypoxia-induced retinal neovascularization via the HIF-1α/VEGF signaling pathway[J].Drug Des Devel Ther,2016,23(10):3071-3081.
[15]Jain RK,Duda DG,Clark JW,et al.Lessons from phase III clinical trials on anti-VEGF therapy for cancer[J].Nat Clin Pract Oncol,2006,3(1):24-40.
[16]Kim K,Yoshida D,Teramoto A.Expression of hypoxia-inducible factor 1alpha and vascular endothelial growth factor in pituitary adenomas[J].Endocr Pathol,2005,16(2):115-121.
[2]Tao Xiaofeng,Liu Chang.Correlation between hypoxia-factor 1α/vascular endothelial growth and the differentiation and invasion of hepatocellular carcinoma[J].General Medicine,2011,14(1):164.[陶晓峰,刘畅.HIF-1α和血管内皮生长因子与肝细胞癌分化及其侵袭性的相关性研究[J].中国全科医学,2011,14(1):164.]
[3]Xie W,Wang H,He Y,et al.CDK5 and its activator P35 in normal pituitary and in pituitary adenomas:Relationship to VEGF expression[J].Int J Biol Sci,2014,10(2):192-199.
[4]Ruggeri RM,Costa G,Simone A,et al.Cell proliferation parameters and apoptosis indices in pituitary macroadenomas[J].J Endocrinol Invest,2012,35(5):473-478.
[5]Wang A,Carberry N,Solli E,et al.Metastatic mantle cell lymphoma to the pituitary gland:Case report and literature review[J].Case Rep Oncol,2016,9(1):25-32.
[6]Selman WR,Laws ER Jr,Scheithauer BW,et al.The occurrence of dural invasion in pituitary adenomas[J].Comment in J Neurosurg,2012,116(2):269.
[7]Song Wuzhai,Chi Jun,Wang Jing.Hypoxia inducible factor HIF-1alpha and malignant tumor[J].Journal of Military Surgeon in Southwest China,2008,10(1):104-106.[宋武战,池君,汪静.缺氧诱导因子HIF-1α与恶性肿瘤[J].西南军医,2008,10(1):104-106.]
[8]Zheng HL,Yang J,Hou Y,et al.Oligomer procyanidins(F2)isolated from grape seeds inhibits tumor angiogenesis and cell invasion by targeting HIF-1αin vitro[J].Int J Oncol,2015,46(2):708-720.
[9]Kraus A,Grampp S,Goppelt Struebe M,et al.P2Y2R is a direct target of HIF-1αand mediates secretion-dependent cyst growth of renal cyst-forming epithelial cells[J].Purinergic Signal,2016,12(4):687-695.
[10]Zhou Y,Jin G,Mi R,et al.Inhibition of fatty acid synthase suppresses neovascularization via regulating the expression of VEGF-A in glioma[J].J Cancer Res Clin Oncol,2016,142(12):2447-2459.
[11]He W,Huang L,Shen X,et al.Relationship between RSUME and HIF-1α/VEGF-A with invasion of pituitary adenoma[J].Gene,2017,603(3):54-60.
[12]Kun Z,Yuling Y,Dongchun W,et al.HIF-1αinhibition sensitized pituitary adenoma cells to temozolomide by regulating presenilin 1 expression and autophagy[J].Technol Cancer Res Treat,2016,15(6):95-104.
[13]Chen W,Xiao Z,Zhao Y,et al.HIF-1αinhibition sensitizes pituitary adenoma cells to temozolomide by regulating MGMT expression[J].Oncol Rep,2013,30(5):2495-2501.
[14]Wu J,Ke X,Ma N,et al.Formononetin,an active compound of astragalus membranaceus(Fisch)Bunge,inhibits hypoxia-induced retinal neovascularization via the HIF-1α/VEGF signaling pathway[J].Drug Des Devel Ther,2016,23(10):3071-3081.
[15]Jain RK,Duda DG,Clark JW,et al.Lessons from phase III clinical trials on anti-VEGF therapy for cancer[J].Nat Clin Pract Oncol,2006,3(1):24-40.
[16]Kim K,Yoshida D,Teramoto A.Expression of hypoxia-inducible factor 1alpha and vascular endothelial growth factor in pituitary adenomas[J].Endocr Pathol,2005,16(2):115-121.