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

长期以来，人们已经知道抗癌药物的效果取决于靶癌细胞的组织学类型。我们用无血清培养法检测了五种人癌细胞系对顺铂、培洛霉素和阿霉素的敏感性。在测试的细胞系中，唾液腺腺癌细胞系（SAC）在体外显示出比鳞状细胞癌细胞系（SCC）对顺铂更敏感。另一方面，SCC对培洛霉素和阿霉素的敏感性高于SAC，已知这些药物是通过被动转运系统摄取的。我们推测，这些药物作用的异质性是由于细胞膜通透性的不同而引起的，而细胞膜通透性的不同应取决于细胞膜脂质的组成。我们发现SCC中70%的膜脂是磷脂。相比之下，SAC中总脂质的80%是中性脂质，如甘油三酯。SAC的中性脂质水平升高，导致细胞膜流动性降低，这与顺铂在细胞内的蓄积量增加相一致。而培洛霉素和阿霉素对主要由磷脂组成的细胞膜脂质具有较强的细胞毒性。这些结果表明，癌细胞膜的脂质组成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.