Drewinko B, Patchen M, Yang L Y, Barlogie B
Cancer Res. 1981 Jun;41(6):2328-33.
The lethal effects of a 1-hr treatment with 20 antitumor drugs on proliferating and nonproliferating cultured human colon carcinoma cells (line LoVo) were analyzed quantitatively by the colony-forming technique. Proliferating cells were obtained from exponentially growing cultures, while nonproliferating cells were from cultures in a stationary phase of growth. The 1-hr treatment was intended to approximate serum peak levels after bolus administration. Two agents, cis-platinum and vindesine, were more effective on nonproliferating than on proliferating cells. Mitomycin C, nitrosourea, and dihydroxybisalkylanthracenedione were equally effective on proliferating and nonproliferating cells. The low lethal activity (less than 1 log) of methylglyoxal bis(guanylhydrazone), hycanthone, and vinblastine was similar in proliferating and nonproliferating cells. For most drugs (Adriamycin, rubidazone, bleomycin, maytansine, vincristine, epipodophyllotoxin, fluorouracil, hydroxyurea, methotrexate, and transplantinum) cytotoxicity was significantly less pronounced (or even totally absent) in nonproliferating than in proliferating cells. These results demonstrate the significance of cellular proliferation kinetics in determining sensitivity to antitumor therapy. Nonproliferating human cells have decreased sensitivity to most antitumor agents. An occasional agent may present increased activity to nonproliferating cells; but at best, few agents can be expected to be as effective on nonproliferating as on proliferating cells.
采用集落形成技术，定量分析了20种抗肿瘤药物对增殖和非增殖培养的人结肠癌细胞（LoVo细胞系）进行1小时处理后的致死效应。增殖细胞取自指数生长期培养物，而非增殖细胞取自生长静止期培养物。1小时的处理旨在模拟推注给药后的血清峰值水平。顺铂和长春地辛这两种药物对非增殖细胞的作用比对增殖细胞更有效。丝裂霉素C、亚硝基脲和二羟基双烷基蒽二酮对增殖细胞和非增殖细胞的作用效果相同。甲基乙二醛双（胍腙）、海蒽酮和长春碱的低致死活性（小于1个对数）在增殖细胞和非增殖细胞中相似。对于大多数药物（阿霉素、柔红霉素、博来霉素、美登素、长春新碱、表鬼臼毒素、氟尿嘧啶、羟基脲、甲氨蝶呤和丙卡巴肼），非增殖细胞中的细胞毒性明显低于增殖细胞（甚至完全没有）。这些结果证明了细胞增殖动力学在确定对抗肿瘤治疗敏感性方面的重要性。非增殖的人类细胞对大多数抗肿瘤药物的敏感性降低。偶尔有一种药物可能对非增殖细胞有增强的活性；但充其量，预计很少有药物对非增殖细胞的效果能与增殖细胞一样好。
