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

Junlian Gu; Yufeng Tang; Yanan Liu; Hua Guo; Yue Wang; Lu Cai; Yang Li; Bo Wang

doi:10.1016/j.canlet.2013.10.011

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

Cancer Lett. 2014 Feb 28;343(2):200-9. doi: 10.1016/j.canlet.2013.10.011. Epub 2013 Oct 23.

Authors

Junlian Gu¹, Yufeng Tang², Yanan Liu¹, Hua Guo¹, Yue Wang¹, Lu Cai³, Yang Li⁴, Bo Wang⁵

Affiliations

¹ Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Center, Norman Bethune College of Medicine, Jilin University, Changchun, China.
² Department of Bone and Joint Surgery, First Hospital of Jilin University, Changchun, China.
³ KCHRI at the Department of Pediatrics, University of Louisville, Louisville, USA; Departments of Radiation Oncology, Pharmacology and Toxicology, University of Louisville, Louisville, USA.
⁴ Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Center, Norman Bethune College of Medicine, Jilin University, Changchun, China. Electronic address: [email protected].
⁵ 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].

PMID: 24161623
DOI: 10.1016/j.canlet.2013.10.011

Abstract

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 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.

Keywords: Cisplatin; Drug resistance; P53; SKOV3/DDP; Si-mdm2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Cisplatin / pharmacology*
Drug Resistance, Neoplasm / genetics*
Drug Therapy, Combination
Female
Flow Cytometry
Immunohistochemistry
Mice
Mice, Inbred BALB C
Mice, Nude
Ovarian Neoplasms / therapy
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / metabolism*

Substances

Antineoplastic Agents
Tumor Suppressor Protein p53
Cisplatin