Home » Key Drug Discovery Articles » 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.

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.

Gu J, Tang Y, Liu Y, Guo H, Wang Y, Cai L, Li Y, Wang B.

Cancer Lett. 2014 Feb 28;343(2):200-9.

Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Center, Norman Bethune College of Medicine, Jilin University, Changchun, China and

Department of Bone and Joint Surgery, First Hospital of Jilin University, Changchun, China and

 

KCHRI at the Department of Pediatrics, University of Louisville, Louisville, USA; Departments of Radiation Oncology, Pharmacology and Toxicology, University of Louisville, Louisville, USA and

Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Center, Norman Bethune College of Medicine, Jilin University, Changchun, China. Electronic address: [email protected] and

Departments of Pathology, The Second Clinical Medical School of Inner Mongolia University for the Nationalities (Inner Mongolia General Forestry Hospital), Yakeshi, Inner Mongolia, China. Electronic address: [email protected]

 

Abstract

 

SKOV3/DDP cells urgently require an efficient therapy to improve drug resistance. Here we show a critical role for cisplatin combined withgene 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 HIF-1, 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 © 2013. Published by Elsevier Ireland Ltd. All rights reserved.

 

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