A study of the new drug delivery system using liposome of the same lipid composition as oral cancer cell membrane

很早以前就知道，抗癌药物的疗效取决于靶癌细胞的组织类型。我们用无血清培养法检测了5种人癌细胞对顺铂、培普霉素和阿霉素的敏感性。在所测试的细胞系中，唾液腺癌细胞系(SAC)在体外对顺铂的敏感性高于鳞状细胞癌细胞系(SCC)。另一方面，与SAC相比，SCC对培莱霉素和阿霉素更敏感，已知这些药物是通过被动转运系统摄入的。我们推测，这些药物作用的异质性是由膜透性的差异造成的，而膜透性的差异应由细胞的膜脂组成决定。我们发现鳞状细胞癌中总膜脂的70%是磷脂。相反，SAC中80%的总脂是中性脂类，如甘油三酯。与SCC相比，SAC较高的中性脂水平可能会导致细胞膜流动性下降，这与顺铂的蓄积量较高是一致的。另一方面，培普霉素和阿霉素对SCC表现出较高的细胞毒性，其膜脂主要由磷脂组成。这些结果表明癌细胞膜的脂质成分是决定癌细胞对抗癌药物敏感性的主要因素。

It has long been known that the effect of anti-cancer drug is dependent on the histological type of the target cancer cells. We have examined the sensivity to cisplatin, peplomycin and doxorubicin of five human cancer cell 1ines by growth assay in serum-free culture. Of the cell lines tested, salivery gland adenocarcinoma cell lines (SAC) were shown to be more sensitive to cisplatin than squamous cell carcinoma cell lines (SCC) in vitro. On the other hand, SCC were more sensitive to peplomycin and doxorubicin in conparison to SAC.It is known that these drugs were uptaken into by passive transport system. We have speculated that heterogenecity of these drug effects is resulted from the difference of membrane permiability, which should be determined by membrane lipid composition of the cells. We have found that 70% of total membrane lipid in SCC is phospholipid. In contrast, 80% of total lipid in SAC is neutral lipid such as triglyceride. The higher neutral lipid level of SAC which should have resulted in decreased membrane fluidity, is consistent with the higher accumulation of cisplatin compared SCC.On the other hand, peplomycin and doxorubicin exhibited high cytotoxicity to SCC, which membrane lipid consisted of phospholipid mainly. These results suggested that the lipid composition of cancer cell membrane was major factor determining the sensitivity of cancer cells to anti-cancer drugs.