In vitro and in vivo growth inhibition of drug-resistant ovarian carcinoma cells using a combination of cisplatin and a TRAIL-encoding retrovirus

摘要

Retroviruses encoding the TNF-related apoptosis-inducing ligand (TRAIL) gene were generated by transient transfection of the retrovirus packing cell line BOSC 23 using TRAIL-encoding plasmid. The retrovirus was able to transduce drug-resistant A2780/DDP ovarian carcinoma cells in vitro and induce TRAIL expression in the cells, as detected by western blot assay. Furthermore, the TRAIL protein led to the growth inhibition of the cells via a caspase-activated apoptotic mechanism. It was confirmed that exposure of such cells to cisplatin in combination with the TRAIL-encoding retrovirus resulted in higher anticancer activity in vitro and in the xenograft A2780/DDP tumor in a nude mouse model. This study suggests that chemotherapy in combination with TRAIL gene therapy may be an efficient approach to treat drug-resistant ovarian cancer.