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.