Apelin/APJ系统与肺癌关系研究
摘要
目的:研究G蛋白偶联受体APJ及其内源性配体apelin是否与肺癌的发生发展有关,是否参与肺癌细胞的生长增殖,发现apelin/APJ的新生物学功能,为临床诊断和治疗肺癌以及抗癌药物的开发提供新的思路.
方法:
1.免疫组织化学法:观察APJ在人肿瘤组织中的表达;
2. ELISA:检测肿瘤病人血浆apelin的含量;
3.免疫荧光法:检测人肺腺癌细胞系A549中APJ定位;
4. Western Blot:检测人肺腺癌细胞系A549、胃腺癌细胞系BGC823、肝癌组织中APJ的表达;
5.细胞增殖检测法:CCK-8试剂盒检测apelin-13对肺腺癌细胞系A549增殖的影响.
结果:
1. APJ在肺腺癌、肺鳞癌、子宫肌瘤、肝细胞癌、胃腺癌、宫颈癌、星形细胞瘤的肿瘤细胞中表达较相应癌旁组织明显增加;
2.肺癌、宫颈癌、胃癌病人血浆中apelin的含量高于对照组;
3. APJ在肺腺癌细胞系A549中表达,主要分布于细胞膜与细胞质;
4. APJ在人肺腺癌细胞、胃腺癌细胞、肝癌组织中均有表达,APJ在肺腺癌细胞中表达高于胃腺癌细胞与肝癌组织;
5. Apelin-13能促进肺腺癌细胞系A549增殖,呈时间、浓度依赖关系,其中浓度为1μmol/L、时间为24h作用最明显.
结论:
1.人肺腺癌、肺鳞癌、子宫肌瘤、肝细胞癌、胃腺癌、宫颈癌、星形细胞瘤APJ受体表达明显增加;
2. Apelin/APJ系统通过促进肺癌细胞增殖参与肺癌的发生发展.
Aim:
1. To study the relationship between apelin/APJ system and human lung cancer;
2. To observe the effect of apelin on the proliferation of human lung adenocarcinoma cell line A549.
Methods:
1. The distribution of APJ in human tumor tissues was detected by Immunohistochemistry staining;
2. The plasma apelin level in tumor patients was detected by ELISA;
3. The distribution of APJ in human lung adenocarcinoma cell line A549 was detected by Immunofluorescence;
4. The expression of APJ in human lung adenocarcinoma cell line A549, human gastric adenocarcinoma cell line BGC823 and liver cancer tiusse was detected by Western blot;
5. The effect of apelin-13 on the proliferation human lung adenocarcinoma cell line A549 was detected by CCK-8 assay.
Results:
1. The expression of APJ in cancer cells of lung adenocarcinoma,lung squamous cell carcinoma,hysteromyoma,liver cancer,gastric cancer,cervical carcinoma was higher than noncancerous tissues;
2. The plasma apelin level in lung cancer patients,cervical cancer patients and gastric cancer patients was higher than normal persons;
3. The APJ expressed on the membrane and cytoplasma of human adenocarcinoma cell line A549;
4. The APJ expressed in lung adenocarcinoma cell line A549, gastric adenocarcinoma cell line BCG823 and liver cancer tissue. The expression of APJ in A549 was higer than BGC823 and liver cancer tissue;
5. Apelin-13 promoted the proliferation of A549 cell in concentration and time dependent manner.
Conclusion:
The expression of APJ in cancer cells of lung adenocarcinoma, lung squamous cell carcinoma, hysteromyoma, liver cancer, gastric cancer, cervical carcinoma was higher than noncancerous tissues. Apelin could promote the proliferation of human lung adenocarcinoma cell line A549. Apelin/APJ was probably involved in the pathogenesis of human lung cancer and other tumors.
方法:
1.免疫组织化学法:观察APJ在人肿瘤组织中的表达;
2. ELISA:检测肿瘤病人血浆apelin的含量;
3.免疫荧光法:检测人肺腺癌细胞系A549中APJ定位;
4. Western Blot:检测人肺腺癌细胞系A549、胃腺癌细胞系BGC823、肝癌组织中APJ的表达;
5.细胞增殖检测法:CCK-8试剂盒检测apelin-13对肺腺癌细胞系A549增殖的影响.
结果:
1. APJ在肺腺癌、肺鳞癌、子宫肌瘤、肝细胞癌、胃腺癌、宫颈癌、星形细胞瘤的肿瘤细胞中表达较相应癌旁组织明显增加;
2.肺癌、宫颈癌、胃癌病人血浆中apelin的含量高于对照组;
3. APJ在肺腺癌细胞系A549中表达,主要分布于细胞膜与细胞质;
4. APJ在人肺腺癌细胞、胃腺癌细胞、肝癌组织中均有表达,APJ在肺腺癌细胞中表达高于胃腺癌细胞与肝癌组织;
5. Apelin-13能促进肺腺癌细胞系A549增殖,呈时间、浓度依赖关系,其中浓度为1μmol/L、时间为24h作用最明显.
结论:
1.人肺腺癌、肺鳞癌、子宫肌瘤、肝细胞癌、胃腺癌、宫颈癌、星形细胞瘤APJ受体表达明显增加;
2. Apelin/APJ系统通过促进肺癌细胞增殖参与肺癌的发生发展.
Aim:
1. To study the relationship between apelin/APJ system and human lung cancer;
2. To observe the effect of apelin on the proliferation of human lung adenocarcinoma cell line A549.
Methods:
1. The distribution of APJ in human tumor tissues was detected by Immunohistochemistry staining;
2. The plasma apelin level in tumor patients was detected by ELISA;
3. The distribution of APJ in human lung adenocarcinoma cell line A549 was detected by Immunofluorescence;
4. The expression of APJ in human lung adenocarcinoma cell line A549, human gastric adenocarcinoma cell line BGC823 and liver cancer tiusse was detected by Western blot;
5. The effect of apelin-13 on the proliferation human lung adenocarcinoma cell line A549 was detected by CCK-8 assay.
Results:
1. The expression of APJ in cancer cells of lung adenocarcinoma,lung squamous cell carcinoma,hysteromyoma,liver cancer,gastric cancer,cervical carcinoma was higher than noncancerous tissues;
2. The plasma apelin level in lung cancer patients,cervical cancer patients and gastric cancer patients was higher than normal persons;
3. The APJ expressed on the membrane and cytoplasma of human adenocarcinoma cell line A549;
4. The APJ expressed in lung adenocarcinoma cell line A549, gastric adenocarcinoma cell line BCG823 and liver cancer tissue. The expression of APJ in A549 was higer than BGC823 and liver cancer tissue;
5. Apelin-13 promoted the proliferation of A549 cell in concentration and time dependent manner.
Conclusion:
The expression of APJ in cancer cells of lung adenocarcinoma, lung squamous cell carcinoma, hysteromyoma, liver cancer, gastric cancer, cervical carcinoma was higher than noncancerous tissues. Apelin could promote the proliferation of human lung adenocarcinoma cell line A549. Apelin/APJ was probably involved in the pathogenesis of human lung cancer and other tumors.
引文
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[2] Habata Y, Fujii R, Hosoya M, et al. Apelin, the natural ligand of the orphan receptor APJ, is abundantly secreted in the colostrum [J]. Biochim Biophys Acta, 1999, 1452(1): 25-35.
[3] Medhurst A D, Jennings C A, Robbins M J, et al. Pharmacological and immunohistochemical characterization of the APJ receptor and its endogenous ligand apelin [J]. J Neurochem, 2003, 84(5): 1162-72.
[4] Kleinz M J, Skepper J N, Davenport A P. Immunocytochemical localisation of the apelin receptor, APJ, to human cardiomyocytes, vascular smooth muscle and endothelial cells [J]. Regul Pept, 2005, 126(3): 233-40.
[5] Lee D K, Cheng R, Nguyen T, et al. Characterization of apelin, the ligand for the APJ receptor [J]. J Neurochem, 2000, 74(1): 34-41.
[6] Saavedra J M, Correa F M, Seltzer A, et al. Enhanced angiotensin converting enzyme binding in arteries from spontaneously hypertensive rats [J]. J Hypertens, 1992, 10(11): 1353-9.
[7]高晶,陈临溪. Apelin/APJ系统的研究进展[J].中国心血管病研究, 2008, 6(3): 41-45.
[8] Ringstrom C, Nitert M D, Bennet H, et al. Apelin is a novel islet peptide [J]. Regul Pept, 162(1-3): 44-51.
[9] Dray C, Debard C, Jager J, et al. Apelin and APJ regulation in adipose tissue and skeletal muscle of type 2 diabetic mice and humans [J]. Am J Physiol Endocrinol Metab, 2010, 298(6): E1161-9.
[10] Ziora K, Oswiecimska J, Swietochowska E, et al. Assessment of Serum Apelin Levels in Girls with Anorexia Nervosa [J]. J Clin Endocrinol Metab, 2010, Epub ahead of print.
[11] Zeng X J, Yu S P, Zhang L, et al. Neuroprotective effect of the endogenous neural peptide apelin in cultured mouse cortical neurons [J]. Exp Cell Res, 2010, Epubahead of print.
[12] Kojima Y, Kundu R K, Cox C M, et al. Upregulation of the apelin-APJ pathway promotes neointima formation in the carotid ligation model in mouse [J]. Cardiovasc Res, 2010, Epub ahead of print.
[13] Iturrioz X, Alvear-Perez R, De Mota N, et al. Identification and pharmacological properties of E339-3D6, the first nonpeptidic apelin receptor agonist [J]. FASEB J, 24(5): 1506-17.
[14] De Paepe B, Verstraeten V L, De Potter C R, et al. Growth stimulatory angiotensin II type-1 receptor is upregulated in breast hyperplasia and in situ carcinoma but not in invasive carcinoma [J]. Histochem Cell Biol, 2001, 116(3): 247-54.
[15] Fujimoto Y, Sasaki T, Tsuchida A, et al. Angiotensin II type 1 receptor expression in human pancreatic cancer and growth inhibition by angiotensin II type 1 receptor antagonist [J]. FEBS Lett, 2001, 495(3): 197-200.
[16] Tao Y, Lu Q, Jiang Y R, et al. Apelin in Plasma and Vitreous and in Fibrovascular Retinal Membranes from Patients with Proliferative Diabetic Retinopathy [J]. Invest Ophthalmol Vis Sci, 2010, Epub ahead of print.
[17] Saint-Geniez M, Masri B, Malecaze F, et al. Expression of the murine msr/apj receptor and its ligand apelin is upregulated during formation of the retinal vessels [J]. Mech Dev, 2002, 110(1-2): 183-6.
[18] Sorli S C, Le Gonidec S, Knibiehler B, et al. Apelin is a potent activator of tumour neoangiogenesis [J]. Oncogene, 2007, 26(55): 7692-9.
[19] Masri B, Morin N, Cornu M, et al. Apelin (65-77) activates p70 S6 kinase and is mitogenic for umbilical endothelial cells [J]. FASEB J, 2004, 18(15): 1909-11.
[20] Kalin R E, Kretz M P, Meyer A M, et al. Paracrine and autocrine mechanisms of apelin signaling govern embryonic and tumor angiogenesis [J]. Dev Biol, 2007, 305(2): 599-614.
[21] Wang G, Anini Y, Wei W, et al. Apelin, a new enteric peptide: localization in the gastrointestinal tract, ontogeny, and stimulation of gastric cell proliferation and of cholecystokinin secretion [J]. Endocrinology, 2004, 145(3): 1342-8.
[22] Carmeliet P, Jain R K. Angiogenesis in cancer and other diseases [J]. Nature, 2000, 407(6801): 249-57.
[23] Eyries M, Siegfried G, Ciumas M, et al. Hypoxia-induced apelin expression regulates endothelial cell proliferation and regenerative angiogenesis [J]. Circ Res, 2008, 103(4): 432-40.
[24] Wang Z, Greeley G H, Jr., Qiu S. Immunohistochemical localization of apelin in human normal breast and breast carcinoma [J]. J Mol Histol, 2008, 39(1): 121-4.
[25] Li F, Li L, Qin X, et al. Apelin-induced vascular smooth muscle cell proliferation: the regulation of cyclin D1 [J]. Front Biosci, 2008, 13(3786-92.
[26] Simpkin J C, Yellon D M, Davidson S M, et al. Apelin-13 and apelin-36 exhibit direct cardioprotective activity against ischemia-reperfusion injury [J]. Basic Res Cardiol, 2007, 102(6): 518-28.
[27] Ronkainen V P, Ronkainen J J, Hanninen S L, et al. Hypoxia inducible factor regulates the cardiac expression and secretion of apelin [J]. FASEB J, 2007, 21(8): 1821-30.
[28] Chen M M, Ashley E A, Deng D X, et al. Novel role for the potent endogenous inotrope apelin in human cardiac dysfunction [J]. Circulation, 2003, 108(12): 1432-9.
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