Storch E, Kirchner H, Schirrmacher V
Cancer Immunol Immunother. 1986;23(3):179-84. doi: 10.1007/BF00205647.
The objective of this study was to evaluate if pretreatment with Corynebacterium parvum (C. parvum) augments the effects of interferon (IFN) inducers on survival of DBA/2 mice transplanted with two syngeneic lymphoma variants, the low metastatic Eb and the high metastatic ESb tumor. The involvement of IFN in the treatment effects was investigated. As inducers of IFN-alpha/beta Newcastle disease virus (NDV), polyinosinic-polycytidylic acid (polyI:polyC), and 10-carboxymethyl-9-acridanone (CMA) were injected i.p. at the site of tumor transplantation. The Eb tumor was found to be sensitive to the antiproliferative action of IFN-alpha/beta in vitro. In vivo single injections of each of the inducers retarded growth of the Eb tumor. In C. parvum-pretreated mice the effects of the inducers on survival were markedly increased. There was a correlation between prolonged survival and local IFN levels in response to polyI:polyC or CMA but not upon NDV. Injections of each of the inducers increased cytotoxicity of peritoneal exudate cells against the Eb tumor cells in vitro especially when mice were pretreated with C. parvum. Although other mechanisms cannot be excluded IFN-mediated activation of host defence and also direct antiproliferative effects of endogenously produced IFN seem to be involved in the antitumor effects by these IFN inducers in the Eb model. In the ESb tumor model irrespective of additional pretreatment with C. parvum survival was only slightly prolonged by the treatments and endogenous IFN induction did not result in any real benefit for the animals. When compared with Eb cells the ESb cells were less sensitive to the antiproliferative action of IFN-alpha/beta in vitro and less sensitive to in vitro cytotoxicity by the host cells. Although other mechanisms may additionally be active in vivo the different susceptibility of the Eb and ESb tumor cells to the direct and indirect actions of IFN seems to contribute to the different responsiveness of these tumor cell lines to the treatments with IFN inducers.
本研究的目的是评估用短小棒状杆菌（C. parvum）预处理是否能增强干扰素（IFN）诱导剂对移植了两种同基因淋巴瘤变体（低转移性Eb和高转移性ESb肿瘤）的DBA/2小鼠存活率的影响。研究了IFN在治疗效果中的作用。作为IFN-α/β的诱导剂，新城疫病毒（NDV）、聚肌苷酸-聚胞苷酸（polyI:polyC）和10-羧甲基-9-吖啶酮（CMA）在肿瘤移植部位腹腔注射。发现Eb肿瘤在体外对IFN-α/β的抗增殖作用敏感。体内单次注射每种诱导剂均可延缓Eb肿瘤的生长。在经C. parvum预处理的小鼠中，诱导剂对存活率的影响显著增加。延长的生存期与对polyI:polyC或CMA反应的局部IFN水平之间存在相关性，但对NDV无此相关性。注射每种诱导剂均可增加体外腹腔渗出细胞对Eb肿瘤细胞的细胞毒性，尤其是在小鼠经C. parvum预处理时。尽管不能排除其他机制，但IFN介导的宿主防御激活以及内源性产生的IFN的直接抗增殖作用似乎参与了这些IFN诱导剂在Eb模型中的抗肿瘤作用。在ESb肿瘤模型中，无论是否用C. parvum进行额外预处理，治疗仅略微延长了生存期，内源性IFN诱导对动物没有带来任何实际益处。与Eb细胞相比，ESb细胞在体外对IFN-α/β的抗增殖作用较不敏感，对宿主细胞的体外细胞毒性也较不敏感。尽管其他机制在体内可能也有作用，但Eb和ESb肿瘤细胞对IFN直接和间接作用的不同敏感性似乎导致了这些肿瘤细胞系对IFN诱导剂治疗的不同反应性。
