June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Characterization of retinoblastoma cell lines with carboplatin resistance
Author Affiliations & Notes
  • CHANG SIK CHO
    Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul, Seoul, Korea (the Republic of)
  • SOO LIM CHI
    Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul, Seoul, Korea (the Republic of)
  • Eunkyung Youn
    Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul, Seoul, Korea (the Republic of)
  • Dong Hyun Jo
    Room #215, Research Building, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
  • Jeong Hun Kim
    Ophthalmology, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
    Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
  • Footnotes
    Commercial Relationships   CHANG SIK CHO None; SOO LIM CHI None; Eunkyung Youn None; Dong Hyun Jo None; Jeong Hun Kim None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 1259. doi:
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      CHANG SIK CHO, SOO LIM CHI, Eunkyung Youn, Dong Hyun Jo, Jeong Hun Kim; Characterization of retinoblastoma cell lines with carboplatin resistance. Invest. Ophthalmol. Vis. Sci. 2023;64(8):1259.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The primary treatment option for retinoblastoma, the most common intraocular malignant tumor in children, is intravenous or intra-arterial chemotherapy and focal treatment. Although a primary chemotherapy regimen based on carboplatin, vincristine, and etoposide is usually sufficient, enucleation (the total removal of the eyeball) is still performed in select patients in which the tumor is or has become chemoresistant. In this context, there is a need for the development of effective second-line treatment options for chemoresistant retinoblastoma.
This study attempted to establish and characterize chemoresistant retinoblastoma cell lines to carboplatin. In particular, we tried to find out whether the reasons for resistance are related to drug resistance.

Methods : Two carboplatin-resistant retinoblastoma cells were developed by treating two retinoblastoma cell lines, Y79 and SNUOT-Rb1, with increasing concentrations of carboplatin in a stepwise fashion. The carboplatin-resistant Y79 and SNUOT-Rb1 cells were termed Y79/CBP and SNUOT-Rb1/CBP. The resulting Y79/CBP and SNUOT-Rb1/CBP lines were confirmed to be resistant to carboplatin in vitro and in vivo. Orthotopic transplantation of retinoblastoma cells into mice was performed to evaluate chemoresistance. Cell cycle analysis was performed by FACS. Changes in cell cycle markers were confirmed through western blot assay. And we checked whether these reasons were related to multidrug resistance (MDR) factors.

Results : 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 were increased in the carboplatin-resistant cells. Furthermore, ATPase copper transporting (ATP7) α (ATP7A), ATP7B, ABCB1, ABCC1, ABCC2, and ABCG2 expression was increased in the Y79/CBP cells, and SNUOT-Rb1/CBP cells, suggesting the presence of MDR in the carboplatin-resistant cells.

Conclusions : These carboplatin-resistant cell lines may serve as a useful tool in the study of chemoresistance in retinoblastoma and for the development of potential therapeutics.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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