Egawa S, Tsutsumi M, Konishi Y, Kobari M, Matsuno S, Nagasaki K, Futami H, Yamaguchi K
Growth Factor Division, National Cancer Center Research Institute, Tokyo, Japan.
Gastroenterology. 1995 May;108(5):1526-33. doi: 10.1016/0016-5085(95)90703-3.
BACKGROUND/AIMS: New therapeutic approach is required for pancreatic cancer, one of the most intractable malignancies. The role of angiogenesis in the tumor growth of a Syrian hamster pancreatic cancer cell line HPD-NR, which closely resembles its human counterpart, was investigated.
Angiogenic activity was measured as stimulation of growth of human umbilical vein endothelial cells (HUVEC), and angiogenic factors produced by HPD-NR cells were identified by reverse-transcription polymerase chain reaction and Northern blot analysis. Then in vitro and in vivo antitumor effects of a potent angiogenesis inhibitor, O-(chloroacetylcarbamoyl)fumagillol (AGM-1470), were examined.
The conditioned medium of HPD-NR cells stimulated the growth of HUVEC, and four hamster angiogenic factors were detected with an overexpression of transforming growth factor alpha and vascular endothelial growth factor messenger RNAs. AGM-1470 specifically inhibited the growth of HUVEC and that of HPD-NR tumors in vivo with decreased vascularity of the tumors but not the growth of HPD-NR cells in vitro.
The results suggest that angiogenesis plays an important role in tumor growth of HPD-NR cells and can be a new target of medical therapy for pancreatic cancer.
背景/目的：胰腺癌是最难治疗的恶性肿瘤之一，需要新的治疗方法。本研究调查了血管生成在叙利亚仓鼠胰腺癌细胞系HPD-NR肿瘤生长中的作用，该细胞系与人类胰腺癌细胞极为相似。
通过检测对人脐静脉内皮细胞（HUVEC）生长的刺激来测定血管生成活性，并通过逆转录聚合酶链反应和Northern印迹分析鉴定HPD-NR细胞产生的血管生成因子。然后检测强效血管生成抑制剂O-(氯乙酰氨基甲酰)烟曲霉素（AGM-1470）的体外和体内抗肿瘤作用。
HPD-NR细胞的条件培养基刺激了HUVEC的生长，并检测到四种仓鼠血管生成因子，同时转化生长因子α和血管内皮生长因子信使核糖核酸过表达。AGM-1470特异性抑制HUVEC的生长以及体内HPD-NR肿瘤的生长，肿瘤血管减少，但不抑制体外HPD-NR细胞的生长。
结果表明血管生成在HPD-NR细胞的肿瘤生长中起重要作用，可能成为胰腺癌药物治疗的新靶点。
