Murine double minute 2 siRNA and wild-type p53 gene therapy enhances sensitivity of the SKOV3/DDP ovarian cancer cell line to cisplatin chemotherapy in vitro and in vivo

SKOV3/DDP cells urgently require an efficient therapy to improve drug resistance. Here we show a critical role for cisplatin combined with gene therapy, using transfection of a p53 gene/MDM2-siRNA plasmid, in improving cisplatin sensitivity of SKOV3/DDP cells with a strong inhibition of tumor cell growth in vitro and in vivo. The effects may be associated with enhancement of intracellular platinum accumulation via decreased MDR1/P-gp and improvement of apoptotic resistance via increased P53, PUMA and NOXA expression. The combined therapy may efficiently inhibit cell invasion and migration via deceased HIFI, VEGF, MMP-9 and MMP-2 to suppress malignant progression. These results indicate that cisplatin chemotherapy combined with targeting the MDM2/p53 axis is an attractive strategy to treat SKOV3/DDP cancer. Crown Copyright (c) 2013 Published by Elsevier Ireland Ltd. All rights reserved.