Futami H, Eader L, Back T T, Gruys E, Young H A, Wiltrout R H, Baguley B C
Laboratory of Experimental Immunology, PRI/DynCorp., Inc., National Cancer Institute-Frederick Cancer Research and Development Center, MD 21701-1013.
J Immunother (1991). 1992 Nov;12(4):247-55. doi: 10.1097/00002371-199211000-00005.
Derivatives of xanthenone-4-acetic acid (XAA) have been found to have similar activity to flavone-8-acetic acid against transplantable solid tumors. Some of these compounds were compared to flavone acetic acid (FAA) in their ability to induce cytokines as well as to mediate antitumor effects against murine renal cancer (Renca) and a mouse colon cancer (MCA-38). 5-Methyl-XAA and 5-chloro-XAA proved to be more potent than FAA on a mg/kg basis for induction of the genes for IFN alpha, IFN gamma, and TNF alpha, and for IFN and TNF activities in the sera of treated mice. These effects were sharply dose dependent. On the other hand, 7-methyl-XAA, which has no antitumor activity, did not induce these genes. In addition, 5-methyl-XAA and 5-chloro-XAA but not 7-methyl-XAA synergized with recombinant human interleukin-2 (rhIL-2) for the treatment of Renca and MCA-38. Doses of the active derivatives that failed to induce cytokines also exhibited no therapeutic synergy with rhIL-2. These results suggest that at least some of the antitumor effects of these XAA derivatives are related to their ability to induce cytokines.
已发现呫吨酮 - 4 - 乙酸（XAA）的衍生物对可移植实体瘤具有与黄酮 - 8 - 乙酸相似的活性。将其中一些化合物与黄酮乙酸（FAA）在诱导细胞因子的能力以及介导对小鼠肾癌（Renca）和小鼠结肠癌（MCA - 38）的抗肿瘤作用方面进行了比较。在每毫克/千克的基础上，5 - 甲基 - XAA和5 - 氯 - XAA在诱导IFNα、IFNγ和TNFα基因以及处理小鼠血清中的IFN和TNF活性方面比FAA更有效。这些作用具有明显的剂量依赖性。另一方面，无抗肿瘤活性的7 - 甲基 - XAA不诱导这些基因。此外，5 - 甲基 - XAA和5 - 氯 - XAA而非7 - 甲基 - XAA与重组人白细胞介素 - 2（rhIL - 2）协同作用用于治疗Renca和MCA - 38。未能诱导细胞因子的活性衍生物剂量与rhIL - 2也未表现出治疗协同作用。这些结果表明，这些XAA衍生物的至少一些抗肿瘤作用与其诱导细胞因子的能力有关。
