| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1995: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1994: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
It has long been known that the effect of anti-cancer dug is dependent on the histological type of the target cancer cells. We have examined the sensitivity to cisplatin, peplomycin and doxorubicin of five human cancer cell lines by growth assay in serum-free culture. Of the cell line tested, salivary gland adenocarcinoma cell lines (SAC) were shown to be generally more sennsitive to cisplatin than squamous cell carcnoma cell lines (SCC) in vitro, and SCC were relatively resistant to cisplatine.On the other hand, SCC were more sensitive to peplomycin and doxorubicin in comparison to SAC.It is known that cisplatin, peplomycin and doxorubicin were uptaken in the cells by passive transport system. We have speculated that heterogeneity of these anti-cancer drug effects is correlated with intracellular drug levels, resulted from the difference of membrane permiability of cancer cells. We studied the membrane lipid composition of the cell lines in serum-free medium, which determine the membr
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ane permiability. We have found that 70% of total membrane lipid in SCC is phospholipid and remainder is free cholesterol. On the other hand, 80% of total membrane lipid in SAC is neutral lipid such as triglyceride and esterified cholesterol, and 20% is phosholipid. 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 and the membrane fluidity was higher than that of SAC.These results suggest that the lipid composition of cancer cell membrane is major factor determining the sensitivity of cancer cells to cisplatin, peplomycin and doxorubicin. Thus, we have designed liposome which is comparable to the lipid composition of SCC cell membrane, constucted the liposome-entrapped cisplatin and examined sensitivity to the liposome-entrapped cisplatin of both SCC and SAC by growth assay in serum-free culture. As the result, the liposome-entrapped cisplantin exhibited enhanced cytotoxicity on SCC compare to either cisplatin alone or cisplatin-liposome mixture. Less
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