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Article Open Access

HSV‑TK/GCV can induce cytotoxicity of retinoblastoma cells through autophagy inhibition by activating MAPK/ERK

  • Authors:
    • Quan‑Yong Yi
    • Zhi‑Sha Bai
    • Bin Cai
    • Nan Chen
    • Li‑Shuang Chen
    • Tao Yuan
    • Jing‑Hai Mao
  • View Affiliations / Copyright

    Affiliations: Department of Ophthalmology, Ningbo Eye Hospital, Ningbo, Zhejiang 315040, P.R. China, Ningbo Central Blood Center, Ningbo, Zhejiang 315040, P.R. China, Department of Ophthalmology, The Fourth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510000, P.R. China
    Copyright: © Yi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 682-692
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    Published online on: May 21, 2018
       https://doi.org/10.3892/or.2018.6454
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Abstract

Retinoblastoma is an severe ophthalmic disease and the most common type intraocular malignant tumor, particularly in infants. Currently, few drugs and therapies are available. Gene therapy has been considered to be a potential treatment to cure cancer effectively and Herpes simplex virus type 1 thymidine kinase/ganciclovir (HSV‑TK/GCV) is one type of suicide gene therapy that has been extensively studied. Numerous in vitro and in vivo studied have shown that this system can kill tumor cells, including liver and lung cancer cells. GCV is used as an antiviral drug, and the thymidine kinase, HSV‑TK can phosphorylate GCV to GCV‑TP, a competitive inhibitor of DNA synthesis, instead of guanine‑5'‑triphosphate in the process of DNA synthesis. This process prevents DNA chain elongation causing cell death via apoptosis. However, the toxic effects of HSV‑TK/GCV on retinoblastoma cells remain unknown, and the molecular mechanisms of its therapeutic effects have not been fully elucidated. Our results suggest that HSV‑TK/GCV can significantly cause the death of retinoblastoma cell lines, HXO‑RB44 and Y79. Further studies have reported that this cell death is induced by the inhibition of autophagy by activating the MAPK/ERK (mitogen‑activated protein kinase/ERK) signaling pathway. The mTOR inhibitor Torin1 can partially block the toxic effects of HSV‑TK/GCV on HXO‑RB44 cells. The above results demonstrate that the mechanism undertaken by HSV‑TK/GCV to exhibit therapeutic effects mechanism may inhibit autophagy by activating MAPK/ERK. The findings of the present study may provide novel insight for the exploration of HSV‑TK/GCV in the treatment of retinoblastoma.
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Spandidos Publications style
Yi QY, Bai ZS, Cai B, Chen N, Chen LS, Yuan T and Mao JH: HSV‑TK/GCV can induce cytotoxicity of retinoblastoma cells through autophagy inhibition by activating MAPK/ERK. Oncol Rep 40: 682-692, 2018.
APA
Yi, Q., Bai, Z., Cai, B., Chen, N., Chen, L., Yuan, T., & Mao, J. (2018). HSV‑TK/GCV can induce cytotoxicity of retinoblastoma cells through autophagy inhibition by activating MAPK/ERK. Oncology Reports, 40, 682-692. https://doi.org/10.3892/or.2018.6454
MLA
Yi, Q., Bai, Z., Cai, B., Chen, N., Chen, L., Yuan, T., Mao, J."HSV‑TK/GCV can induce cytotoxicity of retinoblastoma cells through autophagy inhibition by activating MAPK/ERK". Oncology Reports 40.2 (2018): 682-692.
Chicago
Yi, Q., Bai, Z., Cai, B., Chen, N., Chen, L., Yuan, T., Mao, J."HSV‑TK/GCV can induce cytotoxicity of retinoblastoma cells through autophagy inhibition by activating MAPK/ERK". Oncology Reports 40, no. 2 (2018): 682-692. https://doi.org/10.3892/or.2018.6454
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Spandidos Publications style
Yi QY, Bai ZS, Cai B, Chen N, Chen LS, Yuan T and Mao JH: HSV‑TK/GCV can induce cytotoxicity of retinoblastoma cells through autophagy inhibition by activating MAPK/ERK. Oncol Rep 40: 682-692, 2018.
APA
Yi, Q., Bai, Z., Cai, B., Chen, N., Chen, L., Yuan, T., & Mao, J. (2018). HSV‑TK/GCV can induce cytotoxicity of retinoblastoma cells through autophagy inhibition by activating MAPK/ERK. Oncology Reports, 40, 682-692. https://doi.org/10.3892/or.2018.6454
MLA
Yi, Q., Bai, Z., Cai, B., Chen, N., Chen, L., Yuan, T., Mao, J."HSV‑TK/GCV can induce cytotoxicity of retinoblastoma cells through autophagy inhibition by activating MAPK/ERK". Oncology Reports 40.2 (2018): 682-692.
Chicago
Yi, Q., Bai, Z., Cai, B., Chen, N., Chen, L., Yuan, T., Mao, J."HSV‑TK/GCV can induce cytotoxicity of retinoblastoma cells through autophagy inhibition by activating MAPK/ERK". Oncology Reports 40, no. 2 (2018): 682-692. https://doi.org/10.3892/or.2018.6454
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