Phorbol-12-myristate-13-acetate and interferon-gamma synergistic induction of B7-1 expression in ovary carcinoma cells and immunological value
Zhao, X.; Wei, Y.; Peng, Z.
Zhonghua Fu Chan Ke Za Zhi 34(7): 414-416
1999
ISSN/ISBN: 0529-567X PMID: 11360653 Document Number: 502635
To investigate the therapeutic potential of phorbol-12-myristate-13-acetate(PMA) and interferon-gamma(IFN-gamma) by induction of expression of adhesion molecule in mucious cystadenocarcinoma of ovary (MCAS) and other tumor cells. Expression of costimulatory signals(B7-1), major histocompatibility complex(MHC-I, MHC-II) was analysed with flow cytometry. Cytotoxic T lymphocytes(CTL) killing activity and T cell proliferation induced with expression of B7-1 were evaluated by 4-h 51Cr release assay and standard 3HTdR incorporation and scintitation counting. Pretreatment with PMA and then treated with IFN-gamma was able to enhance B7-1 expression on the tumor cell lines with the constitutive B7-1 expression or on B7-1-transfected tumor cells and to induce B7-1 expression on MCAS and some tumor cell lines without constitutive B7-1 expression. However, treatment with IFN-gamma alone failed to induce B7-1 expression on the tumor cell lines. The synergistic effect of PMA combined with IFN-gamma in the induction of B7-1 expression can be anatagonised by H7 [1-(5-isoquinolinesulfonyl)-2-methyl-Piperazine dihydrochloride]. In addition, treatment with PMA combined with IFN-gamma simultaneously induced or enhanced the expression of MHC class I/II on these tumor cell lines. The tumor cells treated by PMA combined with IFN-gamma were able to induce CTL killing activity and T cell proliferation, which is involved in the expression of B7-1. The enhancement or induction of B7-1 expression by IFN-gamma may be dependent on the prior activation of protein kinase by PMA and the induced B7-1 expression on tumor cells may have some therapeutic potential.