Enhanced sensitivity of small cell lung cancer cell lines to cisplatin andetoposide after infection with adeno-associated virus type 2

In previous studies we have reported the sensitisation of human tumour cell s to gamma irradiation and chemotherapeutic drugs upon infection with the h uman non-pathogenic adeno-associated virus type 2 (AAV-2) in vitro and in v ivo. Treatment of small cell lung cancer (SCLC) is consistently hampered by relapses due to the selection of chemotherapy-resistant cell clones. Hence , we were interested to test whether selection of chemotherapy-resistant SC LC cells might be reduced or even prevented if chemotherapy is applied in c ombination with AAV-2 infection. In vitro proliferation assays indicated th at the number of proliferating cells, after combined treatment with cisplat in and etoposide, can be significantly reduced by concomitant AAV-2 infecti on, as compared with treated but non-infected controls. H446 SCLC cells,whi ch show resistance to etoposide/cisplatin chemotherapy (compared with a cel l line which was never chemotherapeutically treated before, like NCI-H209) were significantly more sensitive after AAV-2 infection, suggesting that th e therapeutic efficacy of chemotherapy in SCLC can be enhanced even if the cells are already relatively resistant to chemotherapy. Similarly, in vivo growth of tumours induced by inoculation of SCLC cells into immunocompromis ed nude mice was reduced more efficiently in AAV-2-infected animals compare d with tumours in mice treated with chemotherapeutic drugs alone. These dat a extend and further support our previous reports on AAV functions which mi ght be useful in improving the efficacy of chemotherapeutic drugs used in h uman cancer treatment. (C) 1999 Elsevier Science Ltd. All rights reserved.