Mitchen J, Rago R, Wilding G
Department of Human Oncology, University of Wisconsin Clinical Cancer Center, Madison 53792.
Prostate. 1993;22(1):75-89. doi: 10.1002/pros.2990220110.
Primary epithelial cultures (PECs) derived from normal, benign hyperplastic (BPH), and cancerous human prostate tissue were treated with increasing doses of suramin, and assayed for cell proliferation over a period of days. The suramin IC50 (inhibitory concentration 50%) value was 0.5 to 1.0 x 10(-4) M, whereas doses between 2.5 x 10(-4) and 5 x 10(-4) M resulted in total growth inhibition. This inhibition was reversible by exchange with suramin-free medium up to day 6. Concentrations > or = 5 x 10(-4) M resulted in increased cytotoxicity as exposure time increased. No differential response to suramin could be demonstrated among the prostate PECs derived from different tissues. The established cell lines, PC-3 and DU 145, grown in serum containing medium exhibited IC50s comparable to the PECs grown in serum free medium. EGF, bFGF, alpha, or beta ECGF at the concentrations tested did not reverse suramin inhibition. Increasing concentrations of bovine pituitary extract (BPE) increased cell growth in both the treated and the control cells. However, the percent growth inhibition by suramin at each concentration of BPE remained constant. Flow cytometry examination of cells treated for 7 days with suramin (0-10(-3) M) failed to detect any significant cell cycle alterations compared to control. At high concentrations of suramin (> or = 10(-4) M), large numbers of viable and dead cells were detectable in the medium. The increase in unattached viable cells was most prevalent (80%) in cultures treated with suramin at the time of plating, but also occurred with cells (25-30%) plated hours prior to the addition of suramin. Treatment for several days with low concentrations of suramin (10(-7) to 10(-5) M) transiently enhanced cell growth compared to controls.
将来自正常、良性增生（BPH）和癌性人类前列腺组织的原代表皮培养物（PEC）用递增剂量的苏拉明处理，并在数天内检测细胞增殖情况。苏拉明的IC50（抑制浓度50%）值为0.5至1.0×10⁻⁴ M，而2.5×10⁻⁴至5×10⁻⁴ M的剂量导致完全生长抑制。这种抑制在第6天之前通过更换无苏拉明的培养基是可逆的。浓度≥5×10⁻⁴ M时，随着暴露时间增加，细胞毒性增强。在源自不同组织的前列腺PEC之间未显示出对苏拉明的差异反应。在含血清培养基中生长的既定细胞系PC-3和DU 145表现出与在无血清培养基中生长的PEC相当的IC50。所测试浓度的表皮生长因子（EGF）、碱性成纤维细胞生长因子（bFGF）、α或β内皮细胞生长因子（ECGF）均不能逆转苏拉明的抑制作用。牛垂体提取物（BPE）浓度增加会使处理组和对照组细胞的生长均增加。然而，在每个BPE浓度下，苏拉明的生长抑制百分比保持恒定。与对照组相比，用苏拉明（0至10⁻³ M）处理7天的细胞的流式细胞术检查未检测到任何显著的细胞周期改变。在高浓度苏拉明（≥10⁻⁴ M）时，培养基中可检测到大量活细胞和死细胞。在接种时用苏拉明处理的培养物中，未附着活细胞的增加最为普遍（80%），但在添加苏拉明前数小时接种的细胞中也会出现（25%至30%）。与对照组相比，用低浓度苏拉明（10⁻⁷至10⁻⁵ M）处理数天会短暂增强细胞生长。
