Schwarzbach Matthias H M, Eisold Sven, Burguete Tatiana, Willeke Frank, Klein-Bauernschmitt Petra, Schlehofer Jörg R, Herfarth Christian, Ridder Ruediger, von Knebel Doeberitz Magnus
Department of Surgery, University of Heidelberg, INF 110, Germany.
Int J Oncol. 2002 Jun;20(6):1211-8.
Doxorubicin-based chemotherapy is used in the treatment of sarcomas. Toxic side effects and poor response rates underline the demand for an improvement in current chemotherapeutic protocols. Recently, it has been reported that parvoviruses confer various antineoplastic properties to infected cells, and that adeno-associated virus type 2 (AAV-2) infection sensitizes malignant epithelial cells to radiation- or chemotherapy-based genotoxic treatment. Thus, we analyzed whether AAV-2 infection leads to an improved efficacy of doxorubicin chemotherapy in malignant mesenchymal cells, using 13 human sarcoma cell lines. Therapeutic effects were analyzed by measuring cell viability and proliferation (WST-1, colony forming, and propidium iodide assays). Additionally, permissivity for AAV-2 infection was determined by Southern dot blot analysis. AAV-2 infection strongly increased the efficacy of doxorubicin treatment in rhabdomyo-, fibro-, osteo- and chondrosarcoma cells in a dose-dependent manner. This effect was not observed in liposarcoma and synovial sarcoma cells, although a susceptability to AAV-2 infection was documented. Our results indicate that the sensitization effects towards genotoxic treatment exerted by non-pathogenic AAV-2 infection are not restricted to epithelial malignancies but may also be exploited for the improvement of chemotherapy in patients suffering from rhabdomyo-, fibro-, osteo-, or chondrosarcomas.
基于阿霉素的化疗用于肉瘤的治疗。毒性副作用和低反应率凸显了改进当前化疗方案的必要性。最近，有报道称细小病毒赋予感染细胞多种抗肿瘤特性，并且2型腺相关病毒（AAV-2）感染使恶性上皮细胞对基于放疗或化疗的基因毒性治疗敏感。因此，我们使用13种人类肉瘤细胞系分析了AAV-2感染是否会提高阿霉素化疗对恶性间充质细胞的疗效。通过测量细胞活力和增殖（WST-1、集落形成和碘化丙啶检测）来分析治疗效果。此外，通过Southern斑点印迹分析确定AAV-2感染的允许性。AAV-2感染以剂量依赖的方式显著提高了阿霉素对横纹肌肉瘤、纤维肉瘤、骨肉瘤和软骨肉瘤细胞的治疗效果。在脂肪肉瘤和滑膜肉瘤细胞中未观察到这种效果，尽管已证明它们对AAV-2感染敏感。我们的结果表明，非致病性AAV-2感染对基因毒性治疗产生的致敏作用不仅限于上皮恶性肿瘤，也可用于改善横纹肌肉瘤、纤维肉瘤、骨肉瘤或软骨肉瘤患者的化疗。
