Ghosh S, Roy S, Banerjee M, Maity P
Dept. of Metabolic Regulation, Chittaranjan National Cancer Institute, Kolkata, India.
J Exp Clin Cancer Res. 2004 Dec;23(4):681-90.
In this study the enzyme glutaminase, purified from the ascites fluid of ovarian cancer patients, was analysed for its antiangiogenic activity. Intraperitoneal administration of this enzyme reduces the number of tumor directed capillaries in solid and ascites tumor bearing Swiss mice induced by transplantation of Ehrlich ascites cells. The enzyme has a critical role in regulating the secretion of vascular endothelial growth factor (VEGF) from tumor cell and in turn tumor growth. Glutamine analogue like 6-diazo, 5- oxo L-norleucine (DON) is also found to be effective in regulating vascular endothelial growth factor (VEGF) secretion from tumor cells in vitro. Treatment with enzyme reduced serum VEGF levels of the tumor induced animals. In vitro VEGF production by EAC cells was reduced in a concentration dependent manner in presence of glutamine analogue.
在本研究中,对从卵巢癌患者腹水中纯化得到的谷氨酰胺酶的抗血管生成活性进行了分析。对荷瘤瑞士小鼠腹腔注射该酶,可减少由艾氏腹水癌细胞移植诱导产生的实体瘤和腹水瘤中肿瘤靶向毛细血管的数量。该酶在调节肿瘤细胞血管内皮生长因子(VEGF)的分泌进而调控肿瘤生长方面起着关键作用。还发现谷氨酰胺类似物如6-重氮-5-氧代-L-正亮氨酸(DON)在体外对调节肿瘤细胞血管内皮生长因子(VEGF)的分泌有效。用该酶处理可降低肿瘤诱导动物的血清VEGF水平。在谷氨酰胺类似物存在的情况下,艾氏腹水癌细胞的体外VEGF生成呈浓度依赖性降低。