1999 Fiscal Year Final Research Report Summary
New targeting therapy with complex of liposome, consist of comparable lipid composition of oral cancer cells, and anti-EGF receptor antibody.
| Project/Area Number |
10557191
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Surgical dentistry
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| Research Institution | Hiroshima University |
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Principal Investigator |
TORATANI Shigeaki University Dental Hospital, Hiroshima University, Lecture, 歯学部・付属病院, 講師 (90172220)
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| Co-Investigator(Kenkyū-buntansha) |
OKAMOTO Tetsuji Faculty of Dentistry, Hiroshima University, Professor, 歯学部, 教授 (00169153)
OSAKI Teruhiko Faculty of Dentistry, Hiroshima University, Assistant, 歯学部, 助手 (60243581)
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| Project Period (FY) |
1998 – 1999
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| Keywords | anti-cancer drugs / liposome / anti-EGF receptor antibody / lipid composition / squamous cell / adenocarcinoma derived |
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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, peplomycin doxorubicin and paclitaxel 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 sensitive to cisplatinand paclitaxal 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 permeability of cancer cells. We studied the membrane lipid composition of the cell lines in serum-free medium w
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hich determine the membrane permeability. 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 main]y 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, doxorubicin and paclrtaxel Thus we have designed liposome which is comparable to the lipid composition of SCC cell membrane, constructed the liposome-entrapped cisplatin or peplomycin and examined sensitivity to the liposome-entrapped drug of both SCC and SAC by growth assay in serum-free culture. As the result, the liposome-entrapped drug exhibited enhanced cytotoxicity on SCC compare to either drug alone or drug-liposome mixture. Furthermore it is known that the epidermal growth factor (EGF) receptor overexpress on SCC and SAC. So we prepared antibody to anti-EGF receptor (12-93 MoAb) and examined the cytotoxic effect of the CDDP-entapped liposome conjugated with 12-93 MoAb to NA and HSY. As result, this complex shown enhanced high cytotoxicity to NA and HSY compare CDDP alone. Less
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Research Products
(2 results)
