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

Oncology Reports
Quan-Yong YiJing-Hai Mao

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‑activate...Continue Reading

Methods Mentioned

BETA
transgenic
transfection
fluorescence microscopy
PCR
xenograft

Software Mentioned

GraphPad
GraphPad Prism

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