Carpenter A, Rassam A, Jennings M H, Robinson-Jackson S, Alexander J S, Erkuran-Yilmaz C
Department of Molecular and Cellular Physiology, LSU Health Sciences Center, Shreveport, LA 71130-3932, USA.
Inflamm Res. 2007 Dec;56(12):515-9. doi: 10.1007/s00011-007-7025-2.
This study examines the target specificity of tetrathiomolybdate (ATM), an anti-angiogenic, anti-tumor agent against the viability / proliferation of arterial, venous, capillary endothelial and tumor cells.
Cells were seeded at 10 or 100% density (to measure viability / proliferation respectively) in medium +/- 0-250 uM ATM. Viability and proliferation were measured by metabolic labeling-colorimetry. One-way ANOVA + Bonferroni testing examined base metabolism; Dunnett's testing was used for viability/proliferation.
Venous proliferation showed high ATM sensitivity (50% reduction ~ > or =5 uM ATM, p<0.01), capillary proliferation was inhibited > or =10 uM (p<0.05). Arterial endothelium were less sensitive to ATM, (50% inhibition ~ > or = 20 uM, p<0.01). YPEN-1 were inhibited >50 uM ATM. Capillary viability was inhibited > or =20 microM ATM (p<0.01); venous, arterial and tumor viability show less ATM sensitivity.
Our data suggest that venous and capillary endothelial proliferation are important targets in ATM therapy, but that other vascular segments and tumor cells may be less influenced.
本研究检测抗血管生成抗肿瘤药物四硫代钼酸盐（ATM）对动脉、静脉、毛细血管内皮细胞及肿瘤细胞活力/增殖的靶向特异性。
将细胞以10%或100%的密度接种（分别用于检测活力/增殖）于含或不含0 - 250 μM ATM的培养基中。通过代谢标记比色法检测活力和增殖。采用单因素方差分析+Bonferroni检验检测基础代谢；采用Dunnett检验检测活力/增殖。
静脉增殖对ATM高度敏感（50%降低≥5 μM ATM，p<0.01），毛细血管增殖在≥10 μM时受到抑制（p<0.05）。动脉内皮对ATM敏感性较低（50%抑制≥20 μM，p<0.01）。YPEN - 1在≥50 μM ATM时受到抑制。毛细血管活力在≥20 μM ATM时受到抑制（p<0.01）；静脉、动脉及肿瘤活力对ATM敏感性较低。
我们的数据表明，静脉和毛细血管内皮增殖是ATM治疗的重要靶点，但其他血管段和肿瘤细胞可能受影响较小。
