Consequences of chemoresistance for the herpes simplex virus thymidine kinase/ganciclovir-induced bystander effect in a human small cell lung cancer cell line model.

This paper focuses on the influence of chemoresistance on the herpes simplex virus (HSVtk)/ganciclovir (GCV)-induced bystander effect (BE), as studied in a human small cell lung cancer (SCLC) cell line (GLC(4)) and its sublines with in vitro acquired resistance to adriamycin (GLC(4)/ADR), mitoxantrone (GLC(4)/MITO) and cisplatin (GLC(4)/CDDP). Chemoresistance for adriamycin, mitoxantrone and cisplatin significantly changed GCV sensitivity. A significant BE was found in all GLC(4) cell lines. Compared to the parental GLC(4) cell line, the BE was significantly higher only for the GLC(4)/ADR cell line. No expression of the nucleoside transporters MRP4 and MRP5 was detected. In all cell lines expression of connexin 43 was found, but modulation of gap junctional intercellular communication (GJIC) by 18-a-glycyrrhetinic acid did not significantly change the BE in any of the GLC(4) cell lines. In conclusion, chemoresistance can influence the HSV-tk/GCV-induced BE, which seems not to be related to differences in MRP4/MRP5 expression or to differences in GJIC.