title: 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.
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.
authors.affiliation: Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Center, Norman Bethune College of Medicine, Jilin University, Changchun, China.
authors.forename: Junlian
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Bone and Joint Surgery, First Hospital of Jilin University, Changchun, China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Center, Norman Bethune College of Medicine, Jilin University, Changchun, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Center, Norman Bethune College of Medicine, Jilin University, Changchun, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Center, Norman Bethune College of Medicine, Jilin University, Changchun, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: KCHRI at the Department of Pediatrics, University of Louisville, Louisville, USA; Departments of Radiation Oncology, Pharmacology and Toxicology, University of Louisville, Louisville, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Cai
authors.affiliation: Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Center, Norman Bethune College of Medicine, Jilin University, Changchun, China. Electronic address: lyang@jlu.edu.cn.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: 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: wangqugans@163.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000628:therapy; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin
keywords: Cisplatin; Drug resistance; P53; SKOV3/DDP; Si-mdm2