ROLE OF T-CELLS AND TUMOR-NECROSIS-FACTOR IN ANTITUMOR-ACTIVITY AND TOXICITY OF FLAVONE ACETIC-ACID
ROLE OF T-CELLS AND TUMOR-NECROSIS-FACTOR IN ANTITUMOR-ACTIVITY AND TOXICITY OF FLAVONE ACETIC-ACID
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DOI：
10.1016/0277-5379(90)90056-y
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发表时间：
1990-01-01
影响因子：
8.4
通讯作者：
PARMIANI, G
中科院分区：
文献类型：
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作者：
PRATESI, G;RODOLFO, M;PARMIANI, G
为探讨自然杀伤（NK）细胞和T细胞在黄酮乙酸（FAA）抑制肿瘤生长中的作用，将结肠癌26小鼠移植于正常和无胸腺小鼠皮下。 FAA在正常胸腺小鼠中有活性，但在无胸腺小鼠中无活性（给药动物与对照动物的肿瘤重量之比[T/C %]分别为27%和92%）。 两种小鼠品系中NK细胞活性均增加，表明该淋巴细胞群体在FAA功效中缺乏主要参与。 在正常胸腺小鼠中，肿瘤特异性T细胞被激活，并且在体内消耗淋巴细胞亚群（L3 T4和Lyt 2）后，FAA的肿瘤抑制被废除（T/C %，88%）。 当治疗后注射抗肿瘤坏死因子α（TNF-α）抗体时，FAA的抗肿瘤疗效也降低。 FAA毒性取决于治疗时的肿瘤重量：200 mg/kg剂量下，肿瘤结节小于50 mg的小鼠死亡率为0，大于300 mg的小鼠死亡率为100%。 当在FAA治疗后给予抗TNF-α抗体时，毒性大大降低（3/14只小鼠死亡，而10/15只小鼠死亡）。
To investigate the importance of natural killer (NK) and T cells in the inhibition of tumour growth by flavone acetic acid (FAA), colon 26 murine carcinoma was grafted subcutaneously in euthymic and athymic mice. FAA was active in euthymic but not in athymic mice (ratio between tumour weight in treated vs. control animals [T/C %], 27% and 92%, respectively). NK cell activity was increased in both mouse strains, indicating a lack of major involvement of this lymphocyte population in FAA efficacy. In euthymic mice tumour-specific T cells were activated, and after in vivo depletion of lymphocyte subpopulations (L3T4 and Lyt2), tumour inhibition by FAA was abrogated (T/C %, 88%). Antitumour efficacy of FAA was also reduced when the treatment was followed by injection of antitumour necrosis factor alpha (TNF-alpha) antibodies. FAA toxicity depended on tumour weight at the time of treatment: 200 mg/kg caused 0 and 100% mortality in mice bearing tumour nodules under 50 and over 300 mg, respectively. When anti-TNF-alpha antibodies were given after FAA treatment, the toxicity was greatly reduced (3/14 mice died compared with 10/15).