Klein-Bauernschmitt P, von Knebel Doeberitz M, Ehrbar M, Geletneky K, Kleinschmidt J, Schlehofer J R
Applied Tumour Virology, German Cancer Research Center, Heidelberg.
Eur J Cancer. 1996 Sep;32A(10):1774-80. doi: 10.1016/0959-8049(96)00175-x.
Increasing resistance of tumour cells towards the cytotoxic action of chemotherapeutic drugs is a major limitation in the treatment of cancer patients. The non-pathogenic human adeno-associated viruses (AAV) have been reported to sensitise HeLa cervical cancer cells to gamma irradiation in vivo and in vitro. To test whether these parvoviruses might render other human tumour cells more sensitive towards chemotherapeutic drugs, we analysed the effects of AAV type 2 (AAV-2) infection on established cancer cell lines and freshly explanted tumour biopsies treated with chemotherapeutic agents (e.g. cisplatin). AAV-2 infection significantly increased the cytotoxic activity of chemotherapeutic drugs compared with uninfected controls. AAV-2 infection without concomitant chemotherapeutic treatment had no significant effect on viability of the cells. In nude mice, combined application of AAV-2 infection and chemotherapeutic treatment significantly increased the therapeutic activity on tumours arising from subcutaneously injected tumour cells compared with tumours treated by chemotherapeutics only. These results indicate that AAV-2 infection sensitises human cancer cells towards the cytotoxic action of chemotherapeutic drugs.
肿瘤细胞对化疗药物细胞毒性作用的抗性增加是癌症患者治疗中的一个主要限制。据报道，无致病性的人类腺相关病毒（AAV）可使HeLa宫颈癌细胞在体内和体外对γ射线敏感。为了测试这些细小病毒是否会使其他人类肿瘤细胞对化疗药物更敏感，我们分析了2型腺相关病毒（AAV-2）感染对已建立的癌细胞系以及经化疗药物（如顺铂）处理的新鲜切除的肿瘤活检组织的影响。与未感染的对照相比，AAV-2感染显著增加了化疗药物的细胞毒性活性。未同时进行化疗处理的AAV-2感染对细胞活力没有显著影响。在裸鼠中，与仅接受化疗的肿瘤相比，AAV-2感染与化疗联合应用显著提高了对皮下注射肿瘤细胞产生的肿瘤的治疗活性。这些结果表明，AAV-2感染使人类癌细胞对化疗药物的细胞毒性作用敏感。
