Garbin F, Eckert K, Immenschuh P, Kreuser E D, Maurer H R
Institut für Pharmazie, Freien Universität Berlin, Germany.
Int J Immunopharmacol. 1997 Jun;19(6):323-32. doi: 10.1016/s0192-0561(97)00024-6.
Recent animal studies demonstrate that prothymosin alpha 1 (ProT alpha) enhances the antitumor response by stimulation of mononuclear phagocyte functions. The present study was aimed at characterizing the in vitro effects by ProT alpha on blood monocytes from human colon cancer patients. Purified peripheral blood monocytes were studied in terms of tumor cytostatic ability and cytokine production after incubation with ProT alpha or interferon (rIFN-gamma) and transforming growth factor-beta (TGF beta), used as reference substances. SW620 colon carcinoma cells were used as tumor target cells in growth inhibition experiments. The level of baseline growth inhibitory activity of unstimulated patient's monocytes was significantly lower than that of normal monocytes. The defective antitumor activity of patient monocytes was associated with a higher production of the inhibitory monokines prostaglandin E2 (PGE2) and TGF beta. The stimulation of monocytes by ProT alpha and/or rIFN-gamma elevated the average antitumor activity in all donor groups. The ProT alpha-induced increase was associated with a significantly higher monocytic secretion of IL-1 beta and TNF-alpha. Moreover, the concentrations of TGF beta and PGE2 in the culture supernatants decreased significantly, when patient's monocytes were treated with ProT alpha and/or rIFN-gamma. Additionally, ProT alpha enhanced the diminished antitumor activity of TGF beta-treated normal monocytes. These results suggest that ProT alpha selectively regulates distinct functions of blood monocytes, the effect of this cytokine varying with the parameter and donor population examined. These data provide a rational and biological endpoint for further studies with ProT alpha as an activator of mononuclear function in colon cancer.
近期的动物研究表明，前胸腺素α1（ProTα）可通过刺激单核吞噬细胞功能增强抗肿瘤反应。本研究旨在表征ProTα对人结肠癌患者血液单核细胞的体外作用。在用ProTα或干扰素（rIFN-γ）以及转化生长因子-β（TGFβ）（用作参考物质）孵育后，对纯化的外周血单核细胞的肿瘤细胞抑制能力和细胞因子产生进行了研究。在生长抑制实验中，使用SW620结肠癌细胞作为肿瘤靶细胞。未刺激的患者单核细胞的基线生长抑制活性水平显著低于正常单核细胞。患者单核细胞抗肿瘤活性的缺陷与抑制性单核因子前列腺素E2（PGE2）和TGFβ的较高产生有关。ProTα和/或rIFN-γ对单核细胞的刺激提高了所有供体组的平均抗肿瘤活性。ProTα诱导的增加与IL-1β和TNF-α的单核细胞分泌显著增加有关。此外，当用ProTα和/或rIFN-γ处理患者的单核细胞时，培养上清液中TGFβ和PGE2的浓度显著降低。此外，ProTα增强了经TGFβ处理的正常单核细胞减弱的抗肿瘤活性。这些结果表明，ProTα选择性调节血液单核细胞的不同功能，这种细胞因子的作用因所检测的参数和供体群体而异。这些数据为进一步研究将ProTα作为结肠癌单核功能激活剂提供了合理的生物学终点。
