Matsubara N, Fuchimoto S, Orita K
First Department of Surgery, Okayama University Medical School, Japan.
Pathobiology. 1990;58(3):168-71. doi: 10.1159/000163578.
In this study we examined whether the antiproliferative effects of tumor necrosis factor (TNF)-alpha and beta were associated with the activation of protein kinase C (PKC), using the LoVo human colon cancer cell line which is resistant to both TNFs. In combination with 12-O-tetradecanoylphorbol-13-acetate (TPA), a potent activator of PKC, TNF-alpha caused marked growth inhibition of LoVo cells, but TNF-beta had little antiproliferative effect. There was no difference in the effect when TPA was added 1 h before or 4 h after TNF-alpha administration. A PKC inhibitor, H-7, not only decreased the sensitivity of LoVo cells to TNF-alpha but also caused a slight promotion of cell proliferation and dose-dependently blocked the growth inhibition induced by TNF-alpha and TPA. These results suggested a possible regulatory function of PKC within the TNF-alpha-mediated intracellular signalling pathway. PKC may act at a later stage in the transduction pathway.
在本研究中，我们使用对两种肿瘤坏死因子（TNF）均耐药的LoVo人结肠癌细胞系，检测了肿瘤坏死因子-α（TNF-α）和-β（TNF-β）的抗增殖作用是否与蛋白激酶C（PKC）的激活相关。与PKC的强效激活剂12-O-十四烷酰佛波醇-13-乙酸酯（TPA）联合使用时，TNF-α可显著抑制LoVo细胞的生长，但TNF-β几乎没有抗增殖作用。在TNF-α给药前1小时或给药后4小时添加TPA，效果并无差异。PKC抑制剂H-7不仅降低了LoVo细胞对TNF-α的敏感性，还略微促进了细胞增殖，并剂量依赖性地阻断了TNF-α和TPA诱导的生长抑制。这些结果提示PKC在TNF-α介导的细胞内信号通路中可能具有调节功能。PKC可能在转导通路的后期发挥作用。
