LITHIUM-CHLORIDE POTENTIATES TUMOR NECROSIS FACTOR-MEDIATED CYTO-TOXICITY INVITRO AND INVIVO
LITHIUM-CHLORIDE POTENTIATES TUMOR NECROSIS FACTOR-MEDIATED CYTO-TOXICITY INVITRO AND INVIVO
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DOI：
10.1073/pnas.86.23.9494
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发表时间：
1989-12-01
影响因子：
11.1
通讯作者：
FIERS, W
中科院分区：
文献类型：
--
作者：
BEYAERT, R;VANHAESEBROECK, B;FIERS, W
肿瘤坏死因子（TNF）在体外对几种转化细胞系具有细胞毒性。在LiCl存在下，鼠纤维肉瘤细胞系L929和WEHI 164克隆13对TNF介导的细胞毒性变得敏感> 10倍。人肿瘤细胞系BT 20和HeLa D98/AH 2也响应于LiCl的细胞毒性增强效应。其他单价或二价阳离子不影响TNF介导的细胞毒性。LiCl对TNF细胞毒性的增强作用在很大程度上不依赖于转录，并且LiCl可以在TNF前2小时或TNF后4小时加入细胞中而不丧失有效性。LiCl增加细胞毒性反应的机制似乎不同于放线菌素D或干扰素γ的致敏作用，因为后一种处理克服了几种细胞系的TNF抗性，而LiCl没有。有证据表明，氯化锂的行为，直接或间接，通过TNF-激活磷脂酶A2途径。在裸鼠中，TNF和LiCl的组合导致L929肿瘤的出血性坏死和生长抑制，而单独施用TNF时观察到的效果很小。HeLa D98/AH 2肿瘤也对体内LiCl的增强作用敏感。我们得出结论，氯化锂增强TNF在体外和体内的有效性，结果可能具有治疗意义。
Tumor necrosis factor (TNF) is cytotoxic for several transformed cell lines in vitro. In the presence of LiCI, the murine fibrosarcoma cell lines L929 and WEHI 164 clone 13 became > 10 times more sensitive to TNF-mediated cytotoxicity. The human tumor cell lines BT20 and HeLa D98/AH2 were also responsive to the cytotoxicity-enhancing effect of LiCl. Other monovalent or divalent cations did not affect TNF-mediated cytotoxicity. The potentiating effect of LiCl on TNF cytotoxicity was largely independent of transcription, and LiCl could be added to the cells as early as 2 hr before or as late as 4 hr after TNF without loss of effectiveness. The mechanism by which LiCl increases the cytotoxic response seems to differ from the sensitizing effect of actinomycin D or interferon .gamma., since the latter treatments overcame TNF resistance of several cell lines, whereas LiCl did not. Evidence is presented that LiCl acts, either directly or indirectly, via the TNF-activated phospholipase A2 pathway. In nude mice, a combination of TNF and LiCl led to hemorrhagic necrosis and growth inhibition of L929 tumors, whereas little effect was observed when TNF was administered alone. HeLa D98/AH2 tumors also were sensitive to the potentiating effect of LiCl in vivo. We conclude that LiCl enhances the effectieness of TNF in vitro and in vivo, results that may have therapeutic implications.