体外筛选具有间接抗肿瘤作用机制的药物的方法:黄酮乙酸的杂蒽酮类似物

Lai-Ming Ching, Graeme J. Finlay, Wayne R. Joseph, Bruce C. Baguley
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引用次数: 13

摘要

xanthenone -4-乙酸(XAA)对小鼠实体瘤的作用类似于黄酮乙酸(FAA)。采用18 h 51cr释放法、持续暴露生长抑制法和刺激培养小鼠腹腔巨噬细胞的杀瘤活性来测定甲基取代XAA衍生物的体外活性。巨噬细胞实验确定了5-MeXAA在体内的高生物活性和剂量效力,并且是最准确的体外预测同源物诱导皮下Lewis肺和结肠肿瘤出血性坏死或脾自然杀伤活性的能力。体外免疫刺激可能比直接细胞毒性更适合筛选具有间接抗肿瘤活性机制的化合物。
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In vitro methods for screening agents with an indirect mechanism of antitumour activity: Xanthenone analogues of flavone acetic acid

Xanthenone-4-acetic acid (XAA) resembles flavone acetic acid (FAA) in its effects on solid tumours in mice. The activity of methyl-substituted XAA derivatives in vitro was determined using 18 h 51Cr-release assays, continuous exposure growth inhibition assays and stimulation of tumouricidal activity of cultured murine resident peritoneal macrophages. The macrophage assay identified the high biological activity and dose potency of 5-MeXAA in vivo, and was the most accurate in vitro predictor of the ability of congeners to induce either haemorrhagic necrosis of subcutaneous Lewis lung and colon 38 tumours or splenic natural killer activity. In vitro immune stimulation may be more appropriate than direct cytotoxicity for screening compounds with indirect mechanisms of antitumour activity.

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