Inducible nitric oxide synthase expression is related to angiogenesis, bcl-2 and cell proliferation in hepatocellular carcinoma

被引：20

作者：

Jia-ping Peng

Shu Zheng

Zuo-xiang Xiao

Su-zhan Zhang

机构：

[1] Cancer Inst., Coll. of Med., Zhejiang Univ.

来源：

Journal of Zhejiang University-SCIENCE A | 2003年 / 4卷 / 2期

关键词：

Angiogenesis; Bcl-2; Flow cytometric analyse; Hepatocellular carcinoma; Nitric oxide synthase;

D O I：

10.1631/jzus.2003.0221

中图分类号：

学科分类号：

摘要：

In this study, we examined the expression of inducible nitric oxide synthase (iNOS) and vascular endothelial growth factor (VEGF) by immunohistochemical staining in 76 tissue sections collected from hepatocellular carcinoma (HCC) patients undergoing hepatectomy. Microvascular density (MVD) was determined by counting endothelial cells immunostained using anti-CD34 antibody. We performed DNA-flow cytometric analyses to elucidate the impact of iNOS and VEGF expression on the cell cycle of HCC. Most of the HCC cells that invaded stroma were markedly immunostained by iNOS antibody. The iNOS stain intensity of the liver tissue close to the tumor edge was stronger than that of HCC tissue, and the strongest was the hepatocytes closer to the tumor tissue. However, iNOS expression in 10 normal hepatic samples was undetectable. VEGF positive expression ratio was 84.8% in iNOS positive expression cases, and the ratio was 35.3% in negative cases. There was significant correlation (P=0.000) between iNOS and VEGF expression. Moreover, iNOS expression was significantly associated with bcl-2 and MVD, but without p53 expression. DNA-flow cytometric analyses showed that combined expression of iNOS and VEGF had significant impact on the cell cycle in HCC. PI (Proliferating Index) and SPF (S-phase fraction) in the combined positive expression of iNOS and VEGF group was significantly higher than that in the combined negative group. The present findings suggested that iNOS expression was significantly associated with angiogenesis, bcl-2 and cell proliferation of HCC.

引用

页码：221 / 227

页数：6

共 18 条

[1]

Ambs S., Bennett W.P., Merriam W.G., Ogunfusika M.O., Oser S.M., Khan M.A., Jones R.T., Harris C.C., Vascular endothelial growth factor and nitric oxide synthase expression in human lung cancer and the relation to p53, Br. J. Cancer, 78, 2, pp. 233-239, (1998)

[2]

Del-Brutto O.H., Dolezal M., Castillo P.R., Garcia H.H., Neurocysticercosis and oncogenesis, Archi. Med. Res., 31, 2, pp. 151-155, (2000)

[3]

Dodd F., Limoges M., Boudreau R., Rowden G., Murphy P.R., Too C.K., L-arginine inhibits apoptosis via a NO-dependent mechanism in Nb2 lymphoma cells, J. Cell Biochem., 77, 4, pp. 624-634, (2000)

[4]

Dulak J., Jozkowicz A., Denbinska K.A., Guevara I., Zdzienicka A., Zmudzinska-Grochot D., Florek I., Wojtowicz A., Szuba A., Cooke J.P., Nitric oxide induces the synthesis of vascular endothelial growth factor by rat vascular smooth muscle cells, Arterioscler Thromb. Vasc. Biol., 20, pp. 659-666, (2000)

[5]

Edwards P., Cendan J.C., Topping D.B., Moldawer L.L., MacKay S., Copeland-EM III., Lind D.S., Tumor cell nitric oxide inhibits cell growth in vitro, but stimulates tumorigenesis and experimental lung metastasis in vivo, J. Surg. Res., 63, 1, pp. 49-52, (1996)

[6]

Folkman J., What is the evidence that tumors are angiogenesis dependent, J. Natl. Cancer Inst., 82, pp. 4-6, (1990)

[7]

Gallo O., Masini E., Morbidelli L., Franchi A., Fini-Storchi I., Vergari W.A., Ziche M., Role of nitric oxide in angogenesis and tumor progression head and neck cancer, J. Natl. Cancer Res., 58, pp. 334-341, (1998)

[8]

Klotz T., Bloch W., Jacobs G., Niggemann S., Engelmann U., Addicks K., Immunolocalization of inducible and constitutive nitric oxide synthases in human bladder cancer, Urology, 54, pp. 416-419, (1999)

[9]

Lala P.K., Orucevic A., Role of nitric oxide in tumor progression: Lessons from experimental tumors, Cancer Rev., 17, pp. 91-106, (1998)

[10]

Murata J.I., Tada M., Iggo R.D., Sawamura Y., Shinohe Y., Abe H., Nitric oxide as a carcinogen: Analysis by yeast functional assay of inactivating p53 mutations induced by nitric oxide, Mutation Research, 379, 2, pp. 211-218, (1997)

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