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Treatment of the P815murine mastocytomawith cisplatin oretoposideup-regulatescell-surface Fas(CD95) expression andincreases sensitivityto anti-Fas… Brent A. WilliamsAndrew P. MakrigiannisJonathan Blay1997 год

Treatment of the P815 murine mastocytoma with cisplatin or etoposide up-regulates cell-surface Fas (CD95) expression and increases sensitivity to anti-Fas antibody-mediated cytotoxicity and to lysis by anti-CD3-activated killer-T cells
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Аннотация: We have investigated the effect of pre-treatment with the anti-cancer drugs cisplatin and etoposide on the susceptibility of P815 murine mastocytoma cells to lysis by murine spleen-derived anti-CD3-activated killer-T (AK-T) cells. A 20 hr pre-treatment with cisplatin (0.2–2 μg/ml) or etoposide (0.01–1 μg/ml) rendered P815 cells significantly more sensitive to AK-T cell–mediated lysis in a 4 hr 51Cr-release assay than untreated control tumor cells. At lower concentrations, pre-treatment with cisplatin or etoposide had no direct cytotoxic effects on P815 tumor cells, as measured by the MTT assay. AK-T cell–mediated killing of P815 tumor cells pre-treated with 2 μg/ml cisplatin or 1 μg/ml etoposide was only partially inhibitable by the Ca2+ chelator EGTA, suggesting that the Ca2+-independent Fas (CD95)/Fas ligand cytolytic pathway of AK-T cells contributes to cytotoxicity. In comparison to untreated control P815 cells, 2 μg/ml cisplatin– or 1 μg/ml etoposide–treated P815 cells exhibited increased expression of Fas mRNA and cell-surface Fas, which correlated with increased sensitivity to lysis by AK-T cells. In addition, pre-treatment with cisplatin or etoposide caused P815 tumor cells to become sensitive to the cytotoxic effects of anti-Fas antibody in a 4 hr 51Cr-release assay. Taken together, our results demonstrate that short-term exposure to concentrations of cisplatin and etoposide in the low cytotoxic range and below up-regulates Fas expression by P815 tumor cells, thereby facilitating cytotoxicity mediated through the Fas/Fas ligand cytolytic pathway. Int. J. Cancer 73:416–423, 1997. © 1997 Wiley-Liss, Inc.
Год издания: 1997
Авторы: Brent A. Williams, Andrew P. Makrigiannis, Jonathan Blay, David W. Hoskin
Издательство: Wiley
Источник: International Journal of Cancer
Ключевые слова: Immune Cell Function and Interaction, Mast cells and histamine, Immunotherapy and Immune Responses
Другие ссылки: International Journal of Cancer (PDF)
International Journal of Cancer (HTML)
PubMed (HTML)