title: Annexin V-TRAIL fusion protein is a more sensitive and potent apoptotic inducer for cancer therapy.
abstract: The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising cancer therapeutic agent, which kills cancer cells selectively, while leaving normal cells unharmed. However, the emerging resistance of tumor cells and patients to TRAIL-induced apoptosis limits its further application. In this study, we developed a chimeric protein Annexin V-TRAIL (designated as TP8) with higher efficacy than TRAIL both in vitro and in vivo. In vitro, the EC50 of TP8 on a series of tumor cells was much lower than wild-type TRAIL. Annexin V provided this recombinant protein with higher efficacy, while leaving tumor specificity of TRAIL unchanged since TP8 had no effects on normal cells. In vivo, TP8 effectively suppressed tumor growth and prolonged tumor doubling time and tumor growth delay time in mouse xenografts involving multiple cancer cell types including A549, Colo205 and Bel7402. This study provides a new rational strategy to treat TRAIL-resistant cancers.
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, Nanjing, 210093, P.R. China.
authors.forename: Fan
authors.initials: F
authors.lastname: Qiu
authors.affiliation: Changzhou High-Tech Research Institute of Nanjing University and Jiangsu TargetPharma Laboratories Inc., Changzhou, 213164, P.R. China.
authors.forename: Minjin
authors.initials: M
authors.lastname: Hu
authors.affiliation: Changzhou High-Tech Research Institute of Nanjing University and Jiangsu TargetPharma Laboratories Inc., Changzhou, 213164, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Tang
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, Nanjing, 210093, P.R. China.
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Liu
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, Nanjing, 210093, P.R. China.
authors.forename: Hongqin
authors.initials: H
authors.lastname: Zhuang
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, Nanjing, 210093, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: 1] The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, Nanjing, 210093, P.R. China [2] Changzhou High-Tech Research Institute of Nanjing University and Jiangsu TargetPharma Laboratories Inc., Changzhou, 213164, P.R. China.
authors.forename: Zi-Chun
authors.initials: ZC
authors.lastname: Hua
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000235:genetics / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D005260:Female; D057809:HEK293 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D017304:Annexin A5; D051017:Apoptosis Regulatory Proteins; D011993:Recombinant Fusion Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human