Development of new drug deliverty system with liposome consist of comparable to the lipid composition of oral cancer cancer cell membrane
| Project/Area Number |
08672311
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
TORATANI Shigeaki Hospital of Dental School, HIROSHIMA UNIVERSITY Lecturer, 歯学部・附属病院, 講師 (90172220)
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| Co-Investigator(Kenkyū-buntansha) |
OKAMOTO Tetsuji School of Dentistry, HIROSHIMA UNIVERSITY Professor, 歯学部, 教授 (00169153)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | liposome / lipid composition of membrane / epidermal growth factor receptor / cisplatin / peplomycin / doxorubicin / squamous cell / adenocarcinoma cell derived from salivary gland |
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| Research Abstract |
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 sensitivity to cisplatin, doxorubicin and peplomycin of five human cancer cell lines by growth assay in serum-free culture. Of the cell line tested, slivary gland adenocarcinoma cell lines (SAC) were shown to be generally more sensitive to cisplatin than squmous cell carcinoma cell lines (SCC) in vitro, and SCC were relatively resistant to cisplatin. On the other hand, SCC were more sensitive to doxorubicin and peplomycin in comparison to SAC.It is known that cisplatin, peplomycin and doxorubicin were uptake in the cells by passive transport system. We have speculated that heterogeneity of these anticancer drug effects is correlated with intracellular drug level, 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 membrane
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permiability. We have found that 70% of total membrane lipid in SCC is phosholipid and remainder is free cholesterol. On the other hand, 80% of total membrane lipid in SAC in neutral lipid such as triglyceride and esterified cholesterol, and 20% is phospholipid. The higher neutral lipid level of SAC which should have resulted in decreased membrane fluidity, is consistent with the higher accumulation of cisplatin compared to SCC.On the other hand, doxorubicin and peplomycin exhibited high cytotoxicity to SCC,which membrane lipid consisted of phospholipid mainly and the membrane fluidity was higher than that of SAC.These result suggest that the lipid composition of cancer cell membranes 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, constructed 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 reult, the liposome-entrapped cisplatin exhibited enhanced cytotoxicity on SCC compare to either cisplatin alone or cisplatin-liposome mixture. And we have shown that epidermal growth factor receptor (EGFR) was over-expression on SCC and SAC.Then we made monoclonal antibody (12-93) to EGFR and combined liposome-entrapped cisplatin with anti-EGFR monoclonal antibody with avidin-biotin method. We have examined sensitivity to the liposome united with anti-EGFR monoclonal antibody of both SCC and SAC in vitro. This liposome had a tendency to enhance cytotoxicity on SCC and SAC compare to liposome-entrapped cisplatin. Less
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Report
(3 results)
Research Products
(8 results)
