title: Antitumor effects of PLGA nanoparticles encapsulating the human PNAS-4 gene combined with cisplatin in ovarian cancer.
abstract: Human PNAS-4 (hPNAS-4), as a pro-apoptotic gene, can inhibit tumor growth when overexpressed in some malignant cells. Poly (lactic-co-glycolic acid) (PLGA) was used as a gene transfer vector due to the advantage of sustained release, nontoxicity and biodegradability. In this study, we aimed to investigate the effect of PLGA nanoparticles encapsulating hPNAS-4 combined with cisplatin (DDP) on ovarian carcinoma. Expression of hPNAS-4 was determined by RT-PCR. Mice bearing intraperitoneal ovarian carcinomas were treated with PBS, pVAX-PLGA nanoparticles (P-P), pVAX-hPNAS-4-PLGA nanoparticles (PhP-P), DDP and PhP-P plus DDP, respectively. Intraperitoneal tumors were weighed to assess the antitumor efficacy. The percentage of proliferative cells and apoptotic cells was evaluated by Ki-67 staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. The anti-angiogenic effects were detected by CD31 staining and the alginate-encapsulate assay. Overexpression of hPNAS-4 was detected by RT-PCR in the PhP-P and PhP-P plus DDP groups. PhP-P exerted significant antitumor activity through induction of apoptosis, inhibition of cell proliferation and suppression of angiogenesis, compared with treatment with P-P or PBS alone. The combination of PhP-P with DDP showed enhanced antitumor activity compared with therapy of PhP-P or DDP alone. PLGA encapsulating hPNAS-4 combined with DDP may have promising applications in the therapy of ovarian cancer.
authors.affiliation: Department of Gynecology and Obstetrics, Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second Hospital, State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, PR China.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Qi
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Song
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Tao
authors.initials: T
authors.lastname: Yi
authors.forename: Shuangzhi
authors.initials: S
authors.lastname: Li
authors.forename: Chuan
authors.initials: C
authors.lastname: Xie
authors.forename: Yu
authors.initials: Y
authors.lastname: Zheng
authors.forename: Yu
authors.initials: Y
authors.lastname: Bai
authors.forename: Chuntang
authors.initials: C
authors.lastname: Sun
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects; D019759:Carbon-Nitrogen Lyases; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D019344:Lactic Acid; D051379:Mice; D008819:Mice, Nude; D053769:Nanocapsules; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000628:therapy; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000628:therapy*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D014183:Transplantation, Heterologous; D047368:Tumor Burden
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D019394:Ki-67 Antigen; D053769:Nanocapsules; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D019759:Carbon-Nitrogen Lyases; C000604991:DESI2 protein, human; D002945:Cisplatin