豆蔻酰佛波醇乙酯与γ-干扰素协同诱导肿瘤细胞B_(7-1)表达的临床研究

Phorbol12myristate13acetate and Interferon Synergistic Induction of B7-1 Expression in Ovary Carcinoma Cells and Immunological Value

目的探讨豆蔻酰佛波醇乙酯（ＰＭＡ）和γ干扰素（γＩＦＮ）在卵巢癌及其他肿瘤治疗中的意义。方法用ＰＭＡ＋γＩＦＮ处理的卵巢癌细胞及其他肿瘤细胞用流式细胞仪检测免疫球蛋白超家族糖蛋白的共刺激分子Ｂ７－１、主要组织相容抗原（ＭＨＣⅠ、ＭＨＣⅡ）的表达情况。并采用５１铬（５１Ｃｒ）４小时释放试验及［３Ｈ］胸腺嘧啶渗入法了解Ｂ７－１的表达对细胞毒性Ｔ淋巴细胞（ＣＴＬ）杀伤活性和对Ｔ淋巴细胞增殖的诱导情况。结果预先用ＰＭＡ处理，后用γＩＦＮ处理的肿瘤细胞，能诱导Ｂ７－１表达阳性的伯基特淋巴瘤细胞株或转染Ｂ７－１基因的卵巢粘液性囊腺癌细胞的Ｂ７－１表达增强，能诱导无Ｂ７－１、ＭＨＣⅠ、ＭＨＣⅡ表达的卵巢癌细胞株及其他肿瘤细胞株表达Ｂ７－１及ＭＨＣⅠ、ＭＨＣⅡ，而单独用γＩＦＮ则不能诱导Ｂ７－１表达。ＰＭＡ和γＩＦＮ的这种协同效应能被蛋白激酶抑制剂１（５磺酰基）异喹啉２甲基哌嗪盐酸盐（Ｈ７）阻断。被诱导表达的Ｂ７－１能激活ＣＴＬ的杀伤活性，并能增强Ｔ淋巴细胞的增殖能力。结论γＩＦＮ诱导的Ｂ７－１的表达可能依赖于ＰＭＡ预先激活蛋白激酶Ｃ。诱导Ｂ７－１等的表达对治疗肿瘤有一定的价值。

Objective To investigate the therapeutic potential of phorbol12myristate13acetate(PMA) and interferon(IFN) by induction of expression of adhesion molecule in mucious cystadenocarcinoma of ovary(MCAS) and other tumor cells. Methods Expression of costimulatory signals(B7-1), major histocompatibility complex(MHCMHC) was analysed with flow cytometry. Cytotoxic T lymphocytes(CTL) killing activity and T cell proliferation induced with expression of B7-1 were evaluated by 4h51Cr release assay and standard3 HTdR incorporation and scintitation counting. Results Pretreatment with PMA and then treated with IFN was able to enhance B7-1 expresssion 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, treament with IFN alone failed to induce B7-1 expression on the tumor cell lines. The synergistic effect of PMA combined with IFN in the induction of B7-1 expression can be anatagonised by H7 lfonyl)2methylPiperazine dihydrochloride]. In addition, treatment with PMA combined with IFN simultaneously induced or enhanced the expression of MHC class / on these tumor cell lines. The tumor cells treated by PMA combined with IFN were able to induce CTL killing activity and T cell proliferation, which is involved in the expression of B7-1. Conclusions The enhancement or induction of B7-1 expression by IFN 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.