New drug delivery system for cancer chemotherapy using lipid commpositions characteristic of cancer cell membrane

已知抗癌药物的作用依赖于靶癌细胞的组织学分型。我们推测，这种frug效应的异质性是由于靶细胞膜疏水性的差异造成的。本研究的第一年，我们在无血清培养条件下，对口腔鳞癌细胞（SCC）和涎腺腺癌细胞（SAC）的脂质代谢和脂质组成进行了研究。我们已经发现，总SCC膜脂质的80%是磷脂和20%是游离胆固醇。另一方面，SAC膜总脂质的80%是中性脂质，如甘油三酯和酯化胆固醇，20%是磷脂，这些结果明显地表明SCC膜的脂质组成不同于SAC膜，并且SCC膜的疏水性高于SAC膜。在无血清培养条件下，培洛霉素（PLM）、顺铂（CDDP）和卡铂（CDBCA）对SCC和SAC的细胞毒作用均较强，而顺铂（CDDP）和卡铂（CDBCA）对SAC的细胞毒作用较强，且细胞毒作用与药物浓度有关。这些结果强烈表明抗癌药物的细胞毒性效应取决于癌细胞膜的疏水性。我们目前正计划研究脂质体的作用，脂质体是抗癌药物与膜脂质的复合物，膜脂质与靶细胞膜的脂质组成相同。

It has been known that the effects of anti cancer drug is dependent of histological typing of the target cancer cells. We have speculated that the heterogeneity of the frug effect is resulted from the defference of membrane hydrophobicity of the target cancer cells. One of major factors determine membrace hydrophobicity membrane lipid compositions.On the first research year, we have studied lipid metabolism and lipid compositions of several oral squamous cell carcinoma cells(SCC) and salibary gland derived adenocarcinoma cells(SAC) in serum-free cell culture. We have found that 80% of total SCC membrane lipid is phosphokipid and 20% is free cholesterol. On the other hand, 80% of total SAC membrane lipid is meutral lipid such as trigriceride and eaterified cholesterol, and 20% is phospholipid, these results apparently revealed that the lipid composition of SCC membrane is defferent from that of SAC and suggest that hydrophobicith of SCC membrane is higher than that of SAC membrane.On the second research year, we have studied the effects of bleomycin (BLM), peplomycin(PLM), cis-platinum(CDDP) and carboplatin(CDBCA) on the growth of weveral SCC and SAC in werum-free cell culture, the cytotoxic activities of BLM and PLM on SCC are stronger than these on SAC.On the other hand, the activities of CDDp and CDBCA on SAC are stronger than these on SCC.Furthermore, these activities are dependent on the intra-cellular concentration of the drugs. These results strongly suggest that cytotoxic effect of anticancer drug are dependent on the hydrophobicity of the cancer cell membrane. We are currently planning to study the effect of lipisome that is complexed anticancer drug with membrane lipid which is the same as lipid composition of target cell membrane.