Hromas R, Barlogie B, Swartzendruber D, Drewinko B
Cancer Res. 1983 Mar;43(3):1135-7.
Anguidine, a protein synthesis inhibitor, has been shown previously to induce a reversible arrest of cell progression through all phases of the mitotic cycle without inducing appreciable cell kill. This "frozen" cell cycle state provided protection of Chinese hamster ovary cells against the lethal effects of 1-beta-D-arabinofuranosylcytosine, Adriamycin, hydroxyurea, 5-fluorouracil, and hyperthermia. We now report on the preferential induction of cytostasis by anguidine in normal WI-38 fibroblasts, occurring at one-tenth of the dosage required to inhibit the cycle progression of WI-38 VA13 cells, the SV40 transformant. Pretreatment with anguidine at a concentration producing effective inhibition of normal cell cycle traverse while permitting sustained proliferation of transformed cells resulted in almost complete protection of WI-38 normal cells against the growth-inhibitory effects of 1-beta-D-arabinofuranosylcytosine and Adriamycin, without reducing the antiproliferative effects of these two agents against WI-38 VA13 transformed cells. Thus, this cytokinetic concept of preferential normal tissue protection should be explored in vivo to increase the therapeutic index of cancer chemotherapy.
安圭定，一种蛋白质合成抑制剂，先前已被证明能诱导细胞在有丝分裂周期的所有阶段可逆性停滞，而不会引起明显的细胞死亡。这种“冻结”的细胞周期状态保护了中国仓鼠卵巢细胞免受1-β-D-阿拉伯呋喃糖基胞嘧啶、阿霉素、羟基脲、5-氟尿嘧啶和热疗的致死作用。我们现在报告，安圭定在正常WI-38成纤维细胞中优先诱导细胞生长停滞，其剂量仅为抑制WI-38 VA13细胞（SV40转化细胞系）周期进程所需剂量的十分之一。用能有效抑制正常细胞周期进程同时允许转化细胞持续增殖的浓度的安圭定进行预处理，几乎能完全保护WI-38正常细胞免受1-β-D-阿拉伯呋喃糖基胞嘧啶和阿霉素的生长抑制作用，同时又不降低这两种药物对WI-38 VA13转化细胞的抗增殖作用。因此，这种优先保护正常组织的细胞动力学概念应在体内进行探索，以提高癌症化疗的治疗指数。
