TRAIL与抗癌药物联合使用对人正常细胞的细胞毒性
Cytotoxicity of TRAIL/anticancer drug combinations in human normal cells.
作者信息
Meurette Olivier, Fontaine Anne, Rebillard Amelie, Le Moigne Gwenaelle, Lamy Thierry, Lagadic-Gossmann Dominique, Dimanche-Boitrel Marie-Therese
机构信息
INSERM U620, IFR140, Faculté de Pharmacie, Université de Rennes 1, 2 avenue Prof. Léon Bernard, 35043 Rennes cedex, and Département d'Hématologie, Hôpital Pontchaillou, France.
出版信息
Ann N Y Acad Sci. 2006 Dec;1090:209-16. doi: 10.1196/annals.1378.023.
TRAIL (TNF-alpha-Related Apoptosis-Inducing Ligand) is a promising anticancer agent. In fact, it induces apoptosis in cancer cells and not in most normal cells. Nevertheless, certain cancer cells are resistant to TRAIL-induced apoptosis and this could limit TRAIL's efficiency in cancer therapy. To overcome TRAIL resistance, a combination of TRAIL with chemotherapy could be used in cancer treatment. However, sensitivity of human normal cells to such combinations is not well known. We showed in this study that TRAIL/cisplatin, in contrast to TRAIL/5-fluorouracil, was toxic toward human primary hepatocytes and resting lymphocytes. Furthermore, both combinations are toxic toward PHA-IL2-activated lymphocytes. In contrast, freshly isolated neutrophils are resistant to TRAIL in combination or not with anticancer drugs.
肿瘤坏死因子相关凋亡诱导配体（TRAIL）是一种很有前景的抗癌药物。事实上，它能诱导癌细胞凋亡，而大多数正常细胞则不会。然而，某些癌细胞对TRAIL诱导的凋亡具有抗性，这可能会限制TRAIL在癌症治疗中的效果。为了克服TRAIL抗性，可将TRAIL与化疗联合用于癌症治疗。然而，人类正常细胞对这种联合治疗的敏感性尚不清楚。我们在本研究中表明，与TRAIL/5-氟尿嘧啶相反，TRAIL/顺铂对人原代肝细胞和静息淋巴细胞有毒性。此外，这两种联合治疗对PHA-IL2激活的淋巴细胞均有毒性。相比之下，新鲜分离的中性粒细胞对TRAIL单独或与抗癌药物联合使用均具有抗性。
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