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Nucleolin-aptamer therapy in retinoblastoma: molecular changes and mass spectrometry–based imaging
Amitava Srimany,
Published in Elsevier Inc
2016
Volume: 5
   
Abstract
Retinoblastoma (RB) is an intraocular childhood tumor which, if left untreated, leads to blindness and mortality. Nucleolin (NCL) protein which is differentially expressed on the tumor cell surface, binds ligands and regulates carcinogenesis and angiogenesis. We found that NCL is over expressed in RB tumor tissues and cell lines compared to normal retina. We studied the effect of nucleolin-aptamer (NCL-APT) to reduce proliferation in RB tumor cells. Aptamer treatment on the RB cell lines (Y79 and WERI-Rb1) led to significant inhibition of cell proliferation. Locked nucleic acid (LNA) modified NCL-APT administered subcutaneously (s.c.) near tumor or intraperitoneally (i.p.) in Y79 xenografted nude mice resulted in 26 and 65% of tumor growth inhibition, respectively. Downregulation of inhibitor of apoptosis proteins, tumor miRNA-18a, altered serum cytokines, and serum miRNA-18a levels were observed upon NCL-APT treatment. Desorption electrospray ionization mass spectrometry (DESI MS)-based imaging of cell lines and tumor tissues revealed changes in phosphatidylcholines levels upon treatment. Thus, our study provides proof of concept illustrating NCL-APT-based targeted therapeutic strategy and use of DESI MS-based lipid imaging in monitoring therapeutic responses in RB. © 2016 Official journal of the American Society of Gene & Cell Therapy
About the journal
JournalData powered by TypesetMolecular Therapy - Nucleic Acids
PublisherData powered by TypesetElsevier Inc
ISSN21622531
Open AccessNo
Concepts (84)
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    Antineoplastic agent
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    Aptamer
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    CLUSTERIN
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    Cytochrome c
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    HEAT SHOCK PROTEIN 27
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    LIVIN
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    LOCKED NUCLEIC ACID
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    Messenger rna
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    Microrna
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    MICRORNA 1
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    MICRORNA 152
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    MICRORNA 15A
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    MICRORNA 16
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    MICRORNA 17
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    MICRORNA 18A
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    MICRORNA 19 1
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    MICRORNA 196B
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    MICRORNA 20A
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    MICRORNA 221
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    MICRORNA 330
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    MOLECULAR THERAPY AGENT
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    NUCLEOLIN
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    NUCLEOLIN APTAMER
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    Phosphatidylcholine
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    PROTEIN BAD
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    PROTEIN BCL XL
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    Protein p21
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    SURVIVIN
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    Tumor marker
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    Unclassified drug
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    X LINKED INHIBITOR OF APOPTOSIS
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    Cytokine
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    DICER
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    INHIBITOR OF APOPTOSIS PROTEIN
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    LOCKED NUCLEIC ACID
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    PEPTIDE APTAMER
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    Animal experiment
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    Animal model
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    Animal tissue
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    Antineoplastic activity
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    Article
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    CANCER GENE THERAPY
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    Cancer inhibition
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    CANCER TISSUE
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    Cell proliferation
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    Controlled study
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    DESORPTION ELECTROSPRAY IONIZATION MASS SPECTROMETRY
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    Down regulation
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    Drug efficacy
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    Drug mechanism
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    Drug stability
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    Female
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    Gene expression regulation
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    Gene overexpression
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    Human
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    Human cell
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    Human tissue
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    In vitro study
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    In vivo study
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    LIPID ANALYSIS
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    LIPIDOMICS
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    Lipogenesis
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    Male
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    Mass spectrometry
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    Molecularly targeted therapy
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    Mouse
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    Nonhuman
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    NONVIRAL GENE DELIVERY SYSTEM
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    Priority journal
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    Retinoblastoma
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    RETINOBLASTOMA CELL LINE
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    TUMOR GROWTH INHIBITION RATE
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    Upregulation
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    Animal cell
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    Cell surface
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    Densitometry
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    Electrospray mass spectrometry
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    Flow cytometry
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    IMMUNOBLOTTING
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    Immunohistochemistry
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    Internalization
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    Protein expression
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    RETINA TISSUE
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    Staining