title: Ovarian cancer treatment with a tumor-targeting and gene expression-controllable lipoplex.
abstract: Overexpression of folate receptor alpha (FRα) and high telomerase activity are considered to be the characteristics of ovarian cancers. In this study, we developed FRα-targeted lipoplexes loaded with an hTERT promoter-regulated plasmid that encodes a matrix protein (MP) of the vesicular stomatitis virus, F-LP/pMP(2.5), for application in ovarian cancer treatment. We first characterized the pharmaceutical properties of F-LP/pMP(2.5). The efficient expression of the MP-driven hTERT promoter in SKOV-3 cells was determined after an in-vitro transfection assay, which was significantly increased compared with a non-modified LP/pMP(2.5) group. F-LP/pMP(2.5) treatment significantly inhibited the growth of tumors and extended the survival of mice in a SKOV-3 tumor model compared with other groups. Such an anti-tumor effect was due to the increased expression of MP in tumor tissue, which led to the induction of tumor cell apoptosis, inhibition of tumor cell proliferation and suppression of tumor angiogenesis. Furthermore, a preliminary safety evaluation demonstrated a good safety profile of F-LP/pMP(2.5) as a gene therapy agent. Therefore, FRα-targeted lipoplexes with therapeutic gene expression regulated by an hTERT promoter might be a promising gene therapy agent and a potential translational candidate for the clinical treatment of ovarian cancer.
authors.affiliation: Lab of Aging Research, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China.
authors.forename: Zhi-Yao
authors.initials: ZY
authors.lastname: He
authors.affiliation: Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Deng
authors.affiliation: Lab of Aging Research, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China.
authors.forename: Xia-Wei
authors.initials: XW
authors.lastname: Wei
authors.affiliation: Lab of Aging Research, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China.
authors.forename: Cui-Cui
authors.initials: CC
authors.lastname: Ma
authors.affiliation: Lab of Aging Research, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China.
authors.forename: Min
authors.initials: M
authors.lastname: Luo
authors.affiliation: Lab of Aging Research, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Lab of Aging Research, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China.|The College of Life Science, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Ya-Xiong
authors.initials: YX
authors.lastname: Sang
authors.affiliation: Lab of Aging Research, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liang
authors.affiliation: Lab of Aging Research, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Lab of Aging Research, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China.
authors.forename: Han-Xiao
authors.initials: HX
authors.lastname: Qin
authors.affiliation: Lab of Aging Research, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China.|Department of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Shen
authors.affiliation: Lab of Aging Research, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Lab of Aging Research, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China.
authors.forename: Yan-Tong
authors.initials: YT
authors.lastname: Liu
authors.affiliation: Lab of Aging Research, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Lab of Aging Research, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China.
authors.forename: Yan-Jun
authors.initials: YJ
authors.lastname: Wen
authors.affiliation: Lab of Aging Research, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China.|Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University and Collaborative Innovation Center of Biotherapy, Beijing 100084, China.
authors.forename: Xiao-Ning
authors.initials: XN
authors.lastname: Zhang
authors.affiliation: Lab of Aging Research, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Qian
authors.affiliation: Lab of Aging Research, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China.
authors.forename: Yu-Quan
authors.initials: YQ
authors.lastname: Wei
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D008081:Liposomes; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000473:pathology / Q000628:therapy*; D010957:Plasmids / Q000235:genetics; D014162:Transfection; D018116:Vesiculovirus / Q000235:genetics; D014763:Viral Matrix Proteins / Q000235:genetics
chemical_list: D008081:Liposomes; D014763:Viral Matrix Proteins