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 |
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| Authors: | Junlian Gu Yufeng Tang Yanan Liu Hua Guo Yue Wang Lu Cai Yang Li Bo Wang |
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| Institution: | 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;4. Departments of Radiation Oncology, Pharmacology and Toxicology, University of Louisville, Louisville, USA;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 |
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| 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. |
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| Keywords: | SKOV3/DDP Drug resistance Cisplatin P53 Si-mdm2 |
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