| Co-Investigator(Kenkyū-buntansha) |
MUTSUZAWA Shuji Kanagawa Dental Collge, School of dentistry, Instractor, 歯科部, 助手 (70229459)
MATSUMOTO Goichi Kanagawa Dental Collge, School of dentistry, Instractor, 歯科部, 助手 (60199867)
KOSE Akira Kanagawa Dental Collge, School of dentistry, Instractor, 歯科部, 講師 (70215268)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1995: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
It has been reported that IL-2 induced LAK cells showed the high value of cytotoxicity against antitumor drug resistant cells expressed P-glycoprotein (P-gp). However, it remains unclear that LAK cells are able to recognize the P-gp on certain tumor cell surface. We examined the difference of susceptibility between expressed and non-expressed P-gp, and determined a sort of the population in LAK cells which play a pivotal role in cytotoxicity, In addition, we estimated the relationship between susceptibility of the tumor cells and expression of P-gp or other antigens on their surface toward LAK cells.
[Materials and methods] Target cells : CEM cells (leukemia), KB cells (oral squamous cell carcinoma) and theseresistant cells (CEM/VLB0.1, CEM/VLB1.0 ; P-gp expressed, KB/BLM1.0, KB/CDDP1.0 ; P-gp non-expressed) were used. Effector cells : peripheral blood mononuclear cells of each volunteers cultured with IL-2 (1,000U/ml) for 4days, and then CD16^+ and CD8^+ cells were isolated from unfractionated LAK cells. Cytotoxicity assay : ^<51>Cr release was measured. Flow cytometric analysis : P-gp, MHC class I,class II,LFA-1,2,3ICAM-1, CD44 and Fas were determind on tumor cell surface. Blocking assay : Target cells were treated with anti-MHC class I,CD44 or MRK16 (anti P-gp) mAb.
[Resuls] Unfractionated LAK cells showed significant higher cytotoxicity to non-expressed P-gp more than thier parent cells. CD16^+-LAK cells play a pivotal role to kill CEM/VLB,CD8^+-LAK cells showed higher cytotoxicity to KB/CDDP1.0. The susceptibility of anti-tumor drug resistant cells expressed P-gp were not inhibited by MRK16. In KB/BLM1.0 and KB/CDDP1.0, the susceptibility showed relationship with MHC class I,ICAM-1.
[Discussion] It was suggested that the susceptibility of the tumor cells were not associated with P-gp. These results indicate that efector cells are various population. The susceptibility is depend on a sort of the tumor cells and on the anti-tumor drug.
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