Top

On-line First

Split Viewer

Mol. Cells

Published online August 29, 2022

© The Korean Society for Molecular and Cellular Biology

Establishment and Characterization of Carboplatin-Resistant Retinoblastoma Cell Lines

Chang Sik Cho1 , Dong Hyun Jo2 , Jin Hyoung Kim3 , and Jeong Hun Kim1,4,5,6,*

1Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul 03080, Korea, 2Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul 03080, Korea, 3BIOGENO KOREA, Ltd., Seoul 04376, Korea, 4Department of Ophthalmology, Seoul National University Hospital, Seoul 03080, Korea, 5Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea, 6Institute of Reproductive Medicine and Population, Seoul National University College of Medicine, Seoul 03080, Korea

Correspondence to : steph25@snu.ac.kr

Received: November 5, 2021; Revised: March 2, 2022; Accepted: May 29, 2022

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/.

Abstract

Carboplatin-based chemotherapy is the primary treatment option for the management of retinoblastoma, an intraocular malignant tumor observed in children. The aim of the present study was to establish carboplatin-resistant retinoblastoma cell lines to facilitate future research into the treatment of chemoresistant retinoblastoma. In total, two retinoblastoma cell lines, Y79 and SNUOT-Rb1, were treated with increasing concentrations of carboplatin to develop the carboplatin-resistant retinoblastoma cell lines (termed Y79/CBP and SNUOT-Rb1/CBP, respectively). To verify resistance to carboplatin, the degree of DNA fragmentation and the expression level of cleaved caspase-3 were evaluated in the cells, following carboplatin treatment. In addition, the newly developed carboplatin-resistant retinoblastoma cells formed in vivo intraocular tumors more effectively than their parental cells, even after the intravitreal injection of carboplatin. Interestingly, the proportion of cells in the G0/G1 phase was higher in Y79/CBP and SNUOT-Rb1/CBP cells than in their respective parental cells. In line with these data, the expression levels of cyclin D1 and cyclin D3 were decreased, whereas p18 and p27 expression was increased in the carboplatin-resistant cells. In addition, the expression levels of genes associated with multidrug resistance were increased. Thus, these carboplatin-resistant cell lines may serve as a useful tool in the study of chemoresistance in retinoblastoma and for the development potential therapeutics.

Keywords carboplatin, cell cycle, chemoresistance, multidrug resistance, retinoblastoma

Article

On-line First

Mol. Cells

Published online August 29, 2022

Copyright © The Korean Society for Molecular and Cellular Biology.

Establishment and Characterization of Carboplatin-Resistant Retinoblastoma Cell Lines

Chang Sik Cho1 , Dong Hyun Jo2 , Jin Hyoung Kim3 , and Jeong Hun Kim1,4,5,6,*

1Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul 03080, Korea, 2Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul 03080, Korea, 3BIOGENO KOREA, Ltd., Seoul 04376, Korea, 4Department of Ophthalmology, Seoul National University Hospital, Seoul 03080, Korea, 5Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea, 6Institute of Reproductive Medicine and Population, Seoul National University College of Medicine, Seoul 03080, Korea

Correspondence to:steph25@snu.ac.kr

Received: November 5, 2021; Revised: March 2, 2022; Accepted: May 29, 2022

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/.

Abstract

Carboplatin-based chemotherapy is the primary treatment option for the management of retinoblastoma, an intraocular malignant tumor observed in children. The aim of the present study was to establish carboplatin-resistant retinoblastoma cell lines to facilitate future research into the treatment of chemoresistant retinoblastoma. In total, two retinoblastoma cell lines, Y79 and SNUOT-Rb1, were treated with increasing concentrations of carboplatin to develop the carboplatin-resistant retinoblastoma cell lines (termed Y79/CBP and SNUOT-Rb1/CBP, respectively). To verify resistance to carboplatin, the degree of DNA fragmentation and the expression level of cleaved caspase-3 were evaluated in the cells, following carboplatin treatment. In addition, the newly developed carboplatin-resistant retinoblastoma cells formed in vivo intraocular tumors more effectively than their parental cells, even after the intravitreal injection of carboplatin. Interestingly, the proportion of cells in the G0/G1 phase was higher in Y79/CBP and SNUOT-Rb1/CBP cells than in their respective parental cells. In line with these data, the expression levels of cyclin D1 and cyclin D3 were decreased, whereas p18 and p27 expression was increased in the carboplatin-resistant cells. In addition, the expression levels of genes associated with multidrug resistance were increased. Thus, these carboplatin-resistant cell lines may serve as a useful tool in the study of chemoresistance in retinoblastoma and for the development potential therapeutics.

Keywords: carboplatin, cell cycle, chemoresistance, multidrug resistance, retinoblastoma

Mol. Cells
Sep 30, 2022 Vol.45 No.9, pp. 603~672
COVER PICTURE
The Target of Rapamycin Complex (TORC) is a central regulatory hub in eukaryotes, which is well conserved in diverse plant species, including tomato (Solanum lycopersicum). Inhibition of TORC genes (SlTOR, SlLST8, and SlRAPTOR) by VIGS (virus-induced gene silencing) results in early fruit ripening in tomato. The red/ orange tomatoes are early-ripened TORC-silenced fruits, while the green tomato is a control fruit. Top, left, control fruit (TRV2-myc); top, right, TRV2-SlLST8; bottom, left, TRV2-SlTOR; bottom, right, TRV2-SlRAPTOR(Choi et al., pp. 660-672).

Supplementary File

Share this article on

  • line
  • mail

Related articles in Mol. Cells

Molecules and Cells

eISSN 0219-1032
qr-code Download