Ubenimex treatment enhances the susceptibility of gastric cancer cell lines to lymphokine-activated killer cells.
We investigated the direct effects of ubenimex on the modification of gastric carcinoma cell lines' susceptibility to killer cells, and the mechanism of its action. The susceptibility of both MKN-45 cells and KATO-III cells to LAK cells was enhanced by treatment with ubenimex for 48 h (p < 0.05), and the optimal concentration for this effect was 10 micrograms/ml. The susceptibility of ubenimex treated KATO-III cells to CD3+ LAK cells, especially to those also expressing CD8, was enhanced. DNA synthesis of tumor cells was not impaired by treatment with ubenimex at all concentrations tested. The binding rate of LAK cells and ubenimex-treated KATO-III cells was similar to that between LAK cells and untreated KATO-III cells. Moreover, no alterations in the expression of any antigen related to mononuclear cell-binding to tumor cells were induced by ubenimex. Lysis or the inhibition of DNA synthesis of tumor cells by LAK cell supernatant was enhanced by ubenimex. These results suggested that the mechanism responsible for the augmentation of tumor cell susceptibility by ubenimex may be a result of the alteration of their sensitivity to some Iytic factors released by LAK cells. Thus ubenimex shows not only an indirect host-mediated anti-tumor activity but also a direct effect on tumor cells, modifying their susceptibility to killer cells, and this may explain why ubenimex shows beneficial clinical effects as an adjuvant treatment.
Department of Gastroenterological Surgery, Wakayama Medical College, Japan.
M
M
Iwahashi
H
H
Tanimura
H
H
Yamaue
M
M
Tani
K
K
Noguchi
S
S
Mizobata
T
T
Tsunoda
M
M
Tamai
T
T
Hotta
K
K
Arii
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D015703:Antigens, CD / Q000378:metabolism; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D000903:Antibiotics, Antineoplastic; D015703:Antigens, CD; D007930:Leucine; C012211:ubenimex