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frug效应的异质性是由于靶癌细胞的膜疏水性不同造成的。膜脂组成是决定膜疏水性的主要因素之一。在第一年的研究中，我们在无血清细胞培养中研究了几种口腔鳞状细胞癌（SCC）和唾液腺源性腺癌细胞（SAC）的脂质代谢和脂质组成。我们发现SCC总膜脂的80%是磷脂，20%是游离胆固醇。另一方面，SAC总膜脂的80%为甘油三酯和酯化胆固醇等中性脂质，20%为磷脂，这些结果明显表明SCC膜的脂质组成与SAC不同，表明SCC膜的疏水性高于SAC膜。在第二年的研究中，我们研究了博来霉素（BLM）、培霉素（PLM）、顺铂（CDDP）和卡铂（CDBCA）对几种SCC和SAC在无werum细胞培养中的生长的影响，BLM和PLM对SCC的细胞毒活性强于SAC。CDDp和CDBCA对SAC的活性强于对SCC的活性。此外，这些活性依赖于药物的细胞内浓度。这些结果强烈提示抗癌药物的细胞毒作用依赖于癌细胞膜的疏水性。我们目前正计划研究与靶细胞膜脂质组成相同的膜脂复合抗癌药物脂质体的作用。

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.