Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Establishment and Characterization of Carboplatin-Resistant Retinoblastoma Cell Line

  • Cho, Chang Sik (Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Clinical Research Institute, Seoul National University Hospital) ;
  • Jo, Dong Hyun (Department of Anatomy and Cell Biology, Seoul National University College of Medicine) ;
  • Kim, Jin Hyoung (BIOGENO KOREA, Ltd.) ;
  • Kim, Jeong Hun (Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Clinical Research Institute, Seoul National University Hospital)
  • Received : 2021.11.05
  • Accepted : 2022.05.29
  • Published : 2022.10.31
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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

Acknowledgement

This work was supported by the Development of Platform Technology for Innovative Medical Measurement funded by Korea Research Institute of Standards and Science (KRISS-GP2022-0006), The Bio & Medical Technology Development Program of the National Research Foundation, MSIP (No. 2018M3D1A1058826), and the Seoul National University Hospital Research (No. 04-2019-0280).

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