Zeisig R, Fichtner I, Arndt D, Jungmann S
Central Institute of Cancer Research, Berlin-Buch, Germany.
Anticancer Drugs. 1991 Aug;2(4):411-7. doi: 10.1097/00001813-199108000-00012.
Hexadecylphosphocholine (HPC) and its analogs with a longer alkyl chain (C18 and C20) were examined for antineoplastic activity in the murine tumor models P388 leukemia, B 16 melanoma, the mammary carcinoma C3H and Ca 755, and the human MT-1 mammary tumor in nude mice. The maximum tolerated doses were determined and found to be higher in mice than in rats. The toxicity of the alkylphosphocholines increases with chain length. The murine mammary carcinoma C3H and the human MT-1 mammary carcinoma showed response to HPC whereas the classical screening models did not respond to the synthetic lipids. Furthermore, HPC showed activity in a mitoxantrone-resistant P388 leukemia. Treated/control values between 120 and 160% in survival time could be obtained following a daily application of the lipid. Examination of the activity of possible cleavage products of HPC gave no information about the mechanism of action of the used etherlipids. Liposomes with encapsulated mitoxantrone, formed from alkylphosphocholines, cholesterol and dicetylphosphate had the same activity against P388 mouse leukemia as the free drug. The hemolytic activity of the three lipids tested in vivo was assumed to be related to toxic deaths of single animals; hemolytic activity was observed to be sometimes independent of schedule and dose.
研究了十六烷基磷胆碱（HPC）及其具有更长烷基链（C18和C20）的类似物在小鼠肿瘤模型P388白血病、B16黑色素瘤、C3H乳腺癌和Ca755以及裸鼠人MT-1乳腺肿瘤中的抗肿瘤活性。确定了最大耐受剂量，发现小鼠的最大耐受剂量高于大鼠。烷基磷胆碱的毒性随链长增加而增加。小鼠C3H乳腺癌和人MT-1乳腺癌对HPC有反应，而经典筛选模型对合成脂质无反应。此外，HPC在米托蒽醌耐药的P388白血病中显示出活性。每天应用该脂质后，生存时间的治疗/对照值可在120%至160%之间。对HPC可能的裂解产物活性的研究未提供有关所用醚脂作用机制的信息。由烷基磷胆碱、胆固醇和二鲸蜡基磷酸酯形成的包封米托蒽醌的脂质体对P388小鼠白血病的活性与游离药物相同。体内测试的三种脂质的溶血活性被认为与个别动物的毒性死亡有关；观察到溶血活性有时与给药方案和剂量无关。
