title: PSP94 contributes to chemoresistance and its peptide derivative PCK3145 represses tumor growth in ovarian cancer.
abstract: Tumor drug resistance remains a major challenge in the treatment of cancer. Here, we show that Prostatic secretory protein 94 (PSP94) levels are reduced in ovarian cancer patients with high levels of excision repair cross-complementing 1 (ERCC1), a marker for chemoresistance. We find that PSP94 is decreased in an ovarian cancer drug-resistant cell line, and plays an important role in the development of drug resistance in vitro. Our studies indicate that PSP94 can partially reverse drug resistance in mouse tumor models in vivo and that a PSP94 peptide derivative PCK3145 suppresses chemoresistant cancer cell and tumor growth in vitro and in vivo. Our investigation of the involved molecular mechanisms suggests that PSP94 may confer drug resistance by modulating the Lin28b/Let-7 signaling pathway. We introduce PSP94 and its peptide derivative PCK3145 as potential target to reverse chemoresistance in ovarian cancer and have begun to identify their relevant molecular targets in specific signaling pathways.
authors.affiliation: 1] Department of Biochemistry, School of Medicine, Department of Basic Pharmaceutical Sciences, School of Pharmacy and Mary Babb Randolph Cancer Center, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, West Virginia, USA [2] IcesnowYanyan Bioscience Association, Beijing, China.
authors.forename: B-X
authors.initials: BX
authors.lastname: Yan
authors.affiliation: 1] Department of Biochemistry, School of Medicine, Department of Basic Pharmaceutical Sciences, School of Pharmacy and Mary Babb Randolph Cancer Center, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, West Virginia, USA [2] Johns Hopkins Bloomberg School of Public Health, Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: J-X
authors.initials: JX
authors.lastname: Ma
authors.affiliation: 1] IcesnowYanyan Bioscience Association, Beijing, China [2] Beijing Animal Science Institute, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, School of Medicine, Department of Basic Pharmaceutical Sciences, School of Pharmacy and Mary Babb Randolph Cancer Center, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, West Virginia, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Biochemistry, School of Medicine, Department of Basic Pharmaceutical Sciences, School of Pharmacy and Mary Babb Randolph Cancer Center, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, West Virginia, USA.
authors.forename: H
authors.initials: H
authors.lastname: Riedel
authors.affiliation: Department of Biochemistry, School of Medicine, Department of Basic Pharmaceutical Sciences, School of Pharmacy and Mary Babb Randolph Cancer Center, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, West Virginia, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Mueller
authors.affiliation: Department of Biochemistry, School of Medicine, Department of Basic Pharmaceutical Sciences, School of Pharmacy and Mary Babb Randolph Cancer Center, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, West Virginia, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Remick
authors.affiliation: Department of Biochemistry, School of Medicine, Department of Basic Pharmaceutical Sciences, School of Pharmacy and Mary Babb Randolph Cancer Center, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, West Virginia, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Yu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D035683:MicroRNAs / Q000235:genetics; D008957:Models, Genetic; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D029584:Prostatic Secretory Proteins / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology*; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D047368:Tumor Burden / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004268:DNA-Binding Proteins; C516326:LIN28B protein, human; D035683:MicroRNAs; D010446:Peptide Fragments; D029584:Prostatic Secretory Proteins; D016601:RNA-Binding Proteins; C043076:beta-microseminoprotein; C487931:mirnlet7 microRNA, human; C506581:tigapotide; C071447:ERCC1 protein, human; D004720:Endonucleases; D017239:Paclitaxel