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

Abstract

In previous studies we have reported the sensitisation of human tumour cells to gamma irradiation and chemotherapeutic drugs upon infection with the human non-pathogenic adeno-associated virus type 2 (AAV-2) in vitro and in vivo. 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 SCLC cells might be reduced or even prevented if chemotherapy is applied in combination with AAV-2 infection. In vitro proliferation assays indicated that the number of proliferating cells, after combined treatment with cisplatin and etoposide, can be significantly reduced by concomitant AAV-2 infection, as compared with treated but non-infected controls. H446 SCLC cells, which show resistance to etoposide/cisplatin chemotherapy (compared with a cell line which was never chemotherapeutically treated before, like NCI-H209) were significantly more sensitive after AAV-2 infection, suggesting that the 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 immunocompromised nude mice was reduced more efficiently in AAV-2-infected animals compared with tumours in mice treated with chemotherapeutic drugs alone. These data extend and further support our previous reports on AAV functions which might be useful in improving the efficacy of chemotherapeutic drugs used in human cancer treatment.