title: Efficient inhibition of ovarian cancer by degradable nanoparticle-delivered survivin T34A gene.
abstract: Gene therapy has promising applications in ovarian cancer therapy. Blocking the function of the survivin protein could lead to the growth inhibition of cancer cells. Herein, we used degradable heparin-polyethyleneimine (HPEI) nanoparticles to deliver a dominant-negative human survivin T34A (hs-T34A) gene to treat ovarian cancer. HPEI nanoparticles were characterized and were found to have a dynamic diameter of 66±4.5 nm and a zeta potential of 27.1±1.87 mV. The constructed hs-T34A gene expression plasmid could be effectively delivered into SKOV3 ovarian carcinoma cells by HPEI nanoparticles with low cytotoxicity. Intraperitoneal administration of HPEI/hs-T34A complexes could markedly inhibit tumor growth in a mouse xenograft model of SKOV3 human ovarian cancer. Moreover, according to our results, apparent apoptosis of cancer cells was observed both in vitro and in vivo. Taken together, the prepared HPEI/hs-T34A formulation showed potential applications in ovarian cancer gene therapy.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Du
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, People's Republic of China.
authors.forename: Jiumeng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Oncology, Cancer Center, West China Hospital, Medical School, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, People's Republic of China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, People's Republic of China.
authors.forename: Yujiao
authors.initials: Y
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, People's Republic of China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, People's Republic of China.
authors.forename: Ke
authors.initials: K
authors.lastname: Men
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, People's Republic of China.
authors.forename: Maling
authors.initials: M
authors.lastname: Gou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000008:administration & dosage / Q000235:genetics*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006493:Heparin / Q000737:chemistry; D006801:Humans; D007274:Injections, Intraperitoneal; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D010957:Plasmids / Q000235:genetics; D011094:Polyethyleneimine / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics*; D000077022:Survivin; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage / Q000235:genetics*
chemical_list: D051017:Apoptosis Regulatory Proteins; C512124:HIV-TAT-survivin (T34A) protein; D011993:Recombinant Fusion Proteins; D000077022:Survivin; D054322:tat Gene Products, Human Immunodeficiency Virus; D011094:Polyethyleneimine; D006493:Heparin
keywords: gene therapy; heparin–polyethyleneimine nanoparticles; human survivin T34A; ovarian cancer