PSP94 contributes to chemoresistance and its peptide derivative PCK3145 represses tumor growth in ovarian cancer

B-X Yan; J-X Ma; J Zhang; Y Guo; H Riedel; M D Mueller; S C Remick; J J Yu

doi:10.1038/onc.2013.466

PSP94 contributes to chemoresistance and its peptide derivative PCK3145 represses tumor growth in ovarian cancer

Oncogene. 2014 Nov 6;33(45):5288-94. doi: 10.1038/onc.2013.466. Epub 2013 Nov 4.

Authors

B-X Yan¹, J-X Ma², J Zhang³, Y Guo⁴, H Riedel⁴, M D Mueller⁴, S C Remick⁴, J J Yu⁴

Affiliations

¹ 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.
² 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.
³ 1] IcesnowYanyan Bioscience Association, Beijing, China [2] Beijing Animal Science Institute, Beijing, China.
⁴ 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.

PMID: 24186202
DOI: 10.1038/onc.2013.466

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.

MeSH terms

Animals
Antineoplastic Agents, Phytogenic / pharmacology
Cell Line, Tumor
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism
Drug Resistance, Neoplasm / drug effects
Drug Resistance, Neoplasm / genetics
Endonucleases / genetics
Endonucleases / metabolism
Female
Gene Expression Regulation, Neoplastic
Humans
Immunoblotting
Mice
MicroRNAs / genetics
Models, Genetic
Ovarian Neoplasms / drug therapy*
Ovarian Neoplasms / genetics
Ovarian Neoplasms / metabolism
Paclitaxel / pharmacology
Peptide Fragments / pharmacology*
Prostatic Secretory Proteins / genetics*
Prostatic Secretory Proteins / metabolism
Prostatic Secretory Proteins / pharmacology*
RNA Interference
RNA-Binding Proteins / genetics
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / genetics
Tumor Burden / drug effects*
Xenograft Model Antitumor Assays

Substances

Antineoplastic Agents, Phytogenic
DNA-Binding Proteins
LIN28B protein, human
MicroRNAs
Peptide Fragments
Prostatic Secretory Proteins
RNA-Binding Proteins
beta-microseminoprotein
mirnlet7 microRNA, human
tigapotide
ERCC1 protein, human
Endonucleases
Paclitaxel