Zwi L J, Baguley B C, Gavin J B, Wilson W R
Department of Pathology, University of Auckland School of Medicine, New Zealand.
J Natl Cancer Inst. 1989 Jul 5;81(13):1005-13. doi: 10.1093/jnci/81.13.1005.
Some investigators have suggested that the marked activity of flavone acetic acid (FAA) against advanced solid tumors in mice results from an indirect effect. This study indicates that the critical effect of FAA is irreversible inhibition of tumor blood flow. Perfusion of sc Colon 38 tumors, assessed with H33342 as a fluorescent stain for functional blood vessels, was reduced to 50% of controls within 3 hours of an ip injection of 1.2 mmol of FAA/kg and was completely inhibited by 24 hours. A double-label fluorescence technique demonstrated a significant decrease in blood flow in both sc Colon 38 and im EMT-6/Ak tumors as early as 15 minutes after iv treatment with 1.2 mmol of FAA/kg, with progressively enlarging zones of perfusion failure. The rate of cell death in totally ischemic EMT-6 tumors was shown to be sufficiently rapid to represent a major component of the observed antitumor effect of FAA if the flavonoid acts via inhibition of blood flow. Further, avascular EMT-6/Ak multicellular spheroids growing in the mouse peritoneum are relatively resistant to killing by FAA administered iv or ip, despite extensive infiltration with host immune cells. These results indicate that inhibition of tumor blood flow by FAA is a necessary component of its antitumor activity against solid tumors.
一些研究人员认为，黄酮醋酸（FAA）对小鼠晚期实体瘤具有显著活性是由间接作用所致。本研究表明，FAA的关键作用是对肿瘤血流的不可逆抑制。以H33342作为功能性血管的荧光染料评估皮下接种的结肠38肿瘤的灌注情况，腹腔注射1.2 mmol/kg的FAA后3小时内，灌注减少至对照的50%，24小时时完全被抑制。一种双标记荧光技术表明，静脉注射1.2 mmol/kg的FAA后15分钟，皮下接种的结肠38肿瘤和原位接种的EMT-6/Ak肿瘤的血流均显著减少，灌注衰竭区域逐渐扩大。如果类黄酮通过抑制血流发挥作用，完全缺血的EMT-6肿瘤中的细胞死亡速度足以快到成为观察到的FAA抗肿瘤作用的主要组成部分。此外，尽管有大量宿主免疫细胞浸润，但在小鼠腹膜中生长的无血管EMT-6/Ak多细胞球体对静脉注射或腹腔注射的FAA杀伤相对耐药。这些结果表明，FAA对肿瘤血流的抑制是其对实体瘤抗肿瘤活性的必要组成部分。
