title: Evaluation of in vivo antitumor effects of ANT2 shRNA delivered using PEI and ultrasound with microbubbles.
abstract: Gene therapy using RNA interference can be directed against tumors through various strategies, but has been hindered owing to the inefficiency of non-viral delivery. To evaluate the antitumor effects of adenine nucleotide translocase-2 (ANT2) short hairpin RNA (shRNA) by intraperitoneal injection using the polyethylenimine (PEI) and an ultrasound gene delivery method, human breast carcinoma MDA-MB-231 cells were injected subcutaneously into NOG (NOD/Shi-scid/IL-2Rγ(null)) mice. The results showed greater tumor regression (*P<0.05) as well as an increased survival rate in the group receiving ANT2 shRNA+two types of enhancer relative to the groups receiving ANT2 shRNA without enhancer. These findings demonstrate that the introduction of PEI and ultrasound with SonoVue exerted enhanced antitumor effects in vivo. Although the combination of jet-PEI and ultrasound provided the best results with respect to tumor regression, the antitumor effects from the individual enhancers were approximately equivalent. In addition, we confirmed that there was no toxicity on aspartate aminotransferase and alanine aminotransferase levels in the liver and albumin, blood urea nitrogen or creatine kinase levels in the kidney following the various gene delivery methods.
authors.affiliation: Department of Pathology, Tumor Immunity Medical Research Center, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: D H
authors.initials: DH
authors.lastname: Park
authors.affiliation: 1] Department of Pathology, Tumor Immunity Medical Research Center, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea [2] Department of Parasitology and Tropical Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: B K
authors.initials: BK
authors.lastname: Jung
authors.affiliation: Department of Pathology, Tumor Immunity Medical Research Center, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Y S
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Department of Pathology, Tumor Immunity Medical Research Center, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: J Y
authors.initials: JY
authors.lastname: Jang
authors.affiliation: Department of Pathology, Tumor Immunity Medical Research Center, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: M K
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Department of Pathology, Tumor Immunity Medical Research Center, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: J K
authors.initials: JK
authors.lastname: Lee
authors.affiliation: School of Electronic Electrical Engineering, Sungkyunkwan University, Suwon, Republic of Korea.
authors.forename: H
authors.initials: H
authors.lastname: Park
authors.affiliation: Department of Biomedical Engineering, Yonsei University, Wonju, Gangwon-do, Republic of Korea.
authors.forename: J
authors.initials: J
authors.lastname: Seo
authors.affiliation: Department of Pathology, Tumor Immunity Medical Research Center, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: C W
authors.initials: CW
authors.lastname: Kim
mesh_terms: D033742:Adenine Nucleotide Translocator 2 / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D045744:Cell Line, Tumor / Q000187:drug effects; D018014:Gene Transfer Techniques; D064593:Heterografts; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D051379:Mice; D045423:Microbubbles; D009368:Neoplasm Transplantation; D011094:Polyethyleneimine / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000378:metabolism* / Q000633:toxicity; D014464:Ultrasonic Therapy
chemical_list: D033742:Adenine Nucleotide Translocator 2; D000970:Antineoplastic Agents; D034741:RNA, Small Interfering; D011094:Polyethyleneimine