• 吉林大學(xué)第一醫(yī)院普外科（長(zhǎng)春130021）;

目的  研究血管內(nèi)皮生長(zhǎng)因子（VEGF）、誘導(dǎo)型一氧化氮合酶（iNOS）及內(nèi)皮型一氧化氮合酶（eNOS）在人胃癌表達(dá)的相關(guān)性及與胃癌血管生成的關(guān)系，探討NO和VEGF的相互作用及NO在VEGF促腫瘤生長(zhǎng)中的作用機(jī)理。
方法  應(yīng)用免疫組化方法檢測(cè)34例胃癌組織中VEGF、iNOS和eNOS的表達(dá)及分布，用血管內(nèi)皮細(xì)胞第Ⅷ相關(guān)抗原（FⅧRAg）行免疫特異性染色計(jì)數(shù)腫瘤微血管密度（MVD）。
結(jié)果  34例胃癌組織中，表達(dá)iNOS者占73.5%，表達(dá)eNOS者占82.4%，表達(dá)VEGF者占91.2%； VEGF與iNOS的表達(dá)具有相關(guān)性（P lt;0.005），VEGF與eNOS的表達(dá)則無(wú)相關(guān)性（P gt;0.05）； 表達(dá)VEGF的胃癌其MVD明顯高于不表達(dá)VEGF的胃癌（P lt;0.025），表達(dá)iNOS的胃癌其MVD明顯高于不表達(dá)iNOS的胃癌（P lt;0.05），表達(dá)eNOS的胃癌MVD與不表達(dá)eNOS的胃癌差異無(wú)顯著性意義（P gt;0.05）。
結(jié)論  胃癌組織中MVD隨著VEGF和iNOS表達(dá)的增加而增加，提示兩者對(duì)胃癌的血管生成起促進(jìn)作用； VEGF與iNOS的表達(dá)具有相關(guān)性，提示iNOS在VEGF的生成和發(fā)揮作用過(guò)程中起重要作用。

引用本文： 王廣義,王旭. 人胃癌VEGF和NOS的表達(dá)與腫瘤血管生成的關(guān)系. 中國(guó)普外基礎(chǔ)與臨床雜志, 2004, 11(1): 55-57. doi: 復(fù)制

1. McMahon G. VEGF receptor signaling in tumor angiogenesis[J]. Oncologist, 2000； 5 Suppl 1∶ 3.
2. Ziche M, Morbidelli E, Masini S, et al. Nitric oxide mediates angiogenesis in vivo and endothelial cell growth and migration in vitro promoted by substance P [J]. J Clin Invest, 1994； 94(5)∶ 2036.
3. Mattern J, Koomagi R, Volm M. Coexpression of VEGF and bFGF in human epidermoid lung carcinoma is associated with increased vessel density [J]. Anticancer Res, 1997； 17(3C)∶ 2249.
4. Vermeulen PB, Gasparini G, Fox SB, et al. Quantification of angiogenesis in solid human tumors: an international consensus on the methodology and criteria of evaluation [J]. Eur J Cancer, 1996； 32(14)∶ 2474.
5. 楊毅軍，石景森. VEGF與腫瘤血管生成 [J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2001； 8(3)∶205.
6. Moochhala S, Rajnakova A. Role of nitric oxide in cancer biology [J]. Free Radic Res, 1999； 31(6)∶ 671.
7. Xie K, Fidler IJ. Therapy of cancer metastasis by activation of the inducible nitric oxide synthase [J]. Cancer Metastasis Rev, 1998； 17(1)∶ 55.
8. Thomsen LL, Miles DW. Role of nitric oxide in tumour progression: lessons from human tumours [J]. Cancer Metastasis Rev, 1998； 17(1)∶ 107.
9. Jenkins DC, Charles IG, Thomsen LL, et al. Roles of nitric oxide in tumor growth [J]. Proc Natl Acad Sci USA, 1995； 92(10)∶ 4392.
10. Lala PK, Orucevic A. Role of nitric oxide in tumor progression: lessons from experimental tumors [J]. Cancer Metastasis Rev, 1998; 17(1)∶91.
11. Jozkowicz A, Pankiewicz J, Dulak J, et al. Nitric oxide mediates the mitogenic effects of insulin and vascular endothelial growth factor but not of leptin in endothelial cells [J]. Acta Biochim Pol, 1999; 46(3)∶703.
12. Michel JB. Role of endothelial nitric oxide in the regulation of the vasomotor system [J]. Pathol Biol (Paris), 1998; 46(3)∶ 181.
13. Konopka TE, Barker JE, Bamford TL, et al. Nitric oxide synthase Ⅱ gene disruption: implicatons for tumor growth and vascular endothelial growth factor production [J]. Cancer Res, 2001; 61(7)∶ 3182.
14. Kimura H, Weisz A, Kurashima Y, et al. Hypoxia response element of the human vascular endothelial growth factor gene mediates transcriptional regulation by nitric oxide: control of hypoxiainducible factor1 activity by nitric oxide [J]. Blood， 2000; 95(1)∶ 189.
15. Chavakis E, Dernbach E, Hermann C, et al. Oxidized LDL inhibits vascular eneothelial growth factorinduced endothelial cell migration by an inhibitory effect on the Akt/endothelial nitric oxied synthase pathway [J]. Circulation, 2001; 103(16)∶ 2102.
  1. 1. McMahon G. VEGF receptor signaling in tumor angiogenesis[J]. Oncologist, 2000； 5 Suppl 1∶ 3.
  2. 2. Ziche M, Morbidelli E, Masini S, et al. Nitric oxide mediates angiogenesis in vivo and endothelial cell growth and migration in vitro promoted by substance P [J]. J Clin Invest, 1994； 94(5)∶ 2036.
  3. 3. Mattern J, Koomagi R, Volm M. Coexpression of VEGF and bFGF in human epidermoid lung carcinoma is associated with increased vessel density [J]. Anticancer Res, 1997； 17(3C)∶ 2249.
  4. 4. Vermeulen PB, Gasparini G, Fox SB, et al. Quantification of angiogenesis in solid human tumors: an international consensus on the methodology and criteria of evaluation [J]. Eur J Cancer, 1996； 32(14)∶ 2474.
  5. 5. 楊毅軍，石景森. VEGF與腫瘤血管生成 [J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2001； 8(3)∶205.
  6. 6. Moochhala S, Rajnakova A. Role of nitric oxide in cancer biology [J]. Free Radic Res, 1999； 31(6)∶ 671.
  7. 7. Xie K, Fidler IJ. Therapy of cancer metastasis by activation of the inducible nitric oxide synthase [J]. Cancer Metastasis Rev, 1998； 17(1)∶ 55.
  8. 8. Thomsen LL, Miles DW. Role of nitric oxide in tumour progression: lessons from human tumours [J]. Cancer Metastasis Rev, 1998； 17(1)∶ 107.
  9. 9. Jenkins DC, Charles IG, Thomsen LL, et al. Roles of nitric oxide in tumor growth [J]. Proc Natl Acad Sci USA, 1995； 92(10)∶ 4392.
  10. 10. Lala PK, Orucevic A. Role of nitric oxide in tumor progression: lessons from experimental tumors [J]. Cancer Metastasis Rev, 1998; 17(1)∶91.
  11. 11. Jozkowicz A, Pankiewicz J, Dulak J, et al. Nitric oxide mediates the mitogenic effects of insulin and vascular endothelial growth factor but not of leptin in endothelial cells [J]. Acta Biochim Pol, 1999; 46(3)∶703.
  12. 12. Michel JB. Role of endothelial nitric oxide in the regulation of the vasomotor system [J]. Pathol Biol (Paris), 1998; 46(3)∶ 181.
  13. 13. Konopka TE, Barker JE, Bamford TL, et al. Nitric oxide synthase Ⅱ gene disruption: implicatons for tumor growth and vascular endothelial growth factor production [J]. Cancer Res, 2001; 61(7)∶ 3182.
  14. 14. Kimura H, Weisz A, Kurashima Y, et al. Hypoxia response element of the human vascular endothelial growth factor gene mediates transcriptional regulation by nitric oxide: control of hypoxiainducible factor1 activity by nitric oxide [J]. Blood， 2000; 95(1)∶ 189.
  15. 15. Chavakis E, Dernbach E, Hermann C, et al. Oxidized LDL inhibits vascular eneothelial growth factorinduced endothelial cell migration by an inhibitory effect on the Akt/endothelial nitric oxied synthase pathway [J]. Circulation, 2001; 103(16)∶ 2102.