目的 研究血管內(nèi)皮生長因子(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促腫瘤生長中的作用機(jī)理。
方法 應(yīng)用免疫組化方法檢測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. 中國普外基礎(chǔ)與臨床雜志, 2004, 11(1): 55-57. doi: 復(fù)制
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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 hypoxiainducible factor1 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 factorinduced endothelial cell migration by an inhibitory effect on the Akt/endothelial nitric oxied synthase pathway [J]. Circulation, 2001; 103(16)∶ 2102. |
- 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 hypoxiainducible factor1 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 factorinduced endothelial cell migration by an inhibitory effect on the Akt/endothelial nitric oxied synthase pathway [J]. Circulation, 2001; 103(16)∶ 2102.