Danhauser-Riedl S, Himmelmann A, Steinhauser G, Busch R, Vogler W R, Rastetter J, Berdel W E
Department of Medicine I, Technische Universität, Munich, F.R.G.
J Lipid Mediat. 1990 Sep-Oct;2(5):271-80.
Hexadecylphosphocholine (HPC) was tested in comparison with the membrane-toxic reference ether lipid ET-18-OCH3 for cytotoxic (trypan blue dye exclusion) and cytostatic/antiproliferative [( 3H]thymidine uptake) activity in six cell lines of human hematologic malignancies, six cell lines of human solid tumors and four drug-resistant sublines and their respective non-resistant parent lines in vitro. HPC showed time- and dose-dependent antiproliferative and cytotoxic activity in almost all cell lines, including drug-resistant sublines over a dose range of 2-120 microM and after incubation times of 24, 48 and 72 h. However, ET-18-OCH3 showed a significantly higher activity than HPC, when both compounds were compared on an equimolar basis. The human tumor clonogenic assay confirmed these results. Furthermore, no cross-resistance for HPC with colchicine or methotrexate and partial cross-resistance for HPC with adriamycin was found in cell lines selected for drug resistance. In conclusion, HPC is cytotoxic for neoplastic cells of different histologies including drug-resistant sublines in vitro. Although its cytotoxicity starts at somewhat higher doses when compared to ET-18-OCH3, further testing as an experimental anticancer drug in vivo and comparative cytotoxicity studies with hematopoietic progenitor cells from bone marrow are recommended.
在体外，将十六烷基磷胆碱（HPC）与膜毒性参考醚脂ET-18-OCH3进行比较，检测其对六种人类血液系统恶性肿瘤细胞系、六种人类实体瘤细胞系以及四种耐药亚系及其各自的非耐药亲代细胞系的细胞毒性（台盼蓝染料排除法）和细胞生长抑制/抗增殖活性（[3H]胸腺嘧啶核苷摄取法）。在2-120微摩尔的剂量范围内，以及在24、48和72小时的孵育时间后，HPC在几乎所有细胞系中均表现出时间和剂量依赖性的抗增殖和细胞毒性活性，包括耐药亚系。然而，当以等摩尔浓度比较这两种化合物时，ET-18-OCH3的活性明显高于HPC。人肿瘤克隆形成试验证实了这些结果。此外，在选择的耐药细胞系中，未发现HPC与秋水仙碱或甲氨蝶呤存在交叉耐药性，而HPC与阿霉素存在部分交叉耐药性。总之，HPC在体外对不同组织学类型的肿瘤细胞具有细胞毒性，包括耐药亚系。尽管与ET-18-OCH3相比，其细胞毒性在稍高剂量时才开始出现，但建议将其作为实验性抗癌药物进行进一步的体内试验，并与来自骨髓的造血祖细胞进行比较细胞毒性研究。
