Anti-tumor activity of synthetic alkyllysophospholipids and glycolipids

(1)烷基磷脂1-O-十八烷基-2-O-甲基-甘油-3-磷酸胆碱（ET 18 - 0 Me）在体内具有明显的抗肿瘤作用。本文报道了溶血磷脂类似物的化学合成及其对小鼠肉瘤180（MM 46）的抗肿瘤活性。其中，1-O-十八烷基-2-O-乙酰乙酰甘油-3-磷酸胆碱的抗肿瘤活性与ET 18 - 0 Me相似，但急性毒性较低，静脉注射具有sn-3构型的ET 18 - 0 Me能有效抑制肉瘤180细胞的生长，而sn-1构型的ET 18 - 0 Me对肉瘤180细胞的生长抑制作用则弱于ET 18 - 0 Me。这种立体特异性类似于在它们作为PAF激动剂的活性中观察到的立体特异性。乙酰乙酰化合物是PAF的另一个拮抗剂，在体内显示出类似的立体特异性抗肿瘤作用。这些发现表明，某些烷基溶血磷脂可能通过与PAF受体结合，激活宿主细胞，使其在体内对肿瘤细胞具有细胞抑制作用。 ...更多信息 感受器我们的初步研究结果表明，在这些条件下的责任细胞可能主要是存在于骨髓中的未成熟的巨噬细胞，另一方面，在某些条件下，ET 18 - 0 Me的体内抗肿瘤活性可能通过直接的细胞毒性和/或通过“非特异性”机制调节宿主防御系统来显示。(2)糖脂由化学合成的甘油糖脂组成的脂质体，如1，2-二棕榈基-[<beta>-纤维二糖基-（1 '-&gt;3）]-甘油（Cel-DAG），被发现可增强ICR小鼠对可移植肿瘤细胞（肉瘤180）的保护性免疫。从用Cel-DAG在体内处理的小鼠制备的腹膜渗出液细胞显示出对小鼠白血病细胞系EL-4的体内细胞生长抑制活性。从该制剂中分离的贴壁细胞表现出类似的活性。当用甘油糖脂预处理时，单独的贴壁细胞部分表现出相当弱的细胞抑制活性，并且通过补充非贴壁细胞部分而恢复全部活性。糖脂诱导杀肿瘤作用的能力受胆固醇含量的影响：随着胆固醇含量的增加，活性降低。少

(1) Alkylphospholipids1-0-Octadecyl-2-0-methyl-glycero-3-phosphocholine (ET18-0Me) has been reported to prossess difine anti-tumor effect in vivo. Lysophospholipid analogs were chemically synthesized and their anti-tumor activity against mouse experimental tumor (Sarcoma 180, MM46) were examined. Among them, 1-0-octadecy-2-0-acetoacetyl-glycero-3-phosphocholine was found to show anti-tumor activity similar to ET18-0Me, with less acute toxicity.Intravenous injection of the ET18-0Me with sn-3 configuration retarded the subcutaneous growth of Sarcoma 180 cells effectively, while the growth inhibition by the sn-1 isomer was much less effective. This stereospecificity was similar to that observed in their activities as PAF agonist. The acetoacetyl compound, another PAF aganist, showed similar stereospecific anti-tumor action in vivo. These findings suggest that some alkyl lysophospholipids may activate host cells to a cytostatic stage against tumor cells in vivo through binding to a PAF rec … More eptor. Our preliminary result indicated that the responsible cells under these conditions might primarily be immature macrophages present in the bone-marrow.On the other hand, under some conditions, the in vivo anti-tumor activity of ET18-0Me may be revealed through direct cytotoxicity and/or modulation of host defense system by 'non-specific' mechanisms.(2) GlycolipidsLiposomes composed of chemically synthesized glyceroglycolipids, such as 1,2-dipalmityl-[ <beta> -cellobiosyl-(1'->3)]-glycerol (Cel-DAG), were found to enhance protective immunity against transplatable tumor cells (sarcoma 180) in ICR mice. Peritoneal exudate cells prepared from mice treated in vivo with Cel-DAG showed cytostatic activity in vivo against the mouse leukemia cell line, EL-4. Adherent cells separated from this preparation showed similar activity.The adherent cell fraction alone showed rather weak cytostatic activity when pretreated with the glyceroglycolipids, and full activity was restored by supplementing with the non-adherent cell fraction. The ability of glycolipids to induce tumoricidal effects was affected by cholesterol content: with increasing cholesterol content, the activities decreased. Less