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UNBS5162 inhibits proliferation of human retinoblastoma cells by promoting cell apoptosis

Authors Wang B, Shen J, Wang J

Received 4 July 2017

Accepted for publication 26 September 2017

Published 6 November 2017 Volume 2017:10 Pages 5303—5309

DOI https://doi.org/10.2147/OTT.S145518

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Ashok Kumar Pandurangan

Peer reviewer comments 2

Editor who approved publication: Dr Ingrid Espinoza

Bing Wang, Jiaquan Shen, Jue Wang

Department of Ophthalmology, The Provincial Hospital Affiliated To Shandong University, Jinan, China

Abstract: Human retinoblastomas are malignant intraocular tumors and have a high incidence in children. Chemotherapy combined with local therapy is the principal means of retinoblastoma treatment, the application of which has saved the eye of many children and avoided external irradiation. UNBS5162, a naphthalimide, has broad prospects as a tumor treatment, with fewer toxic side effects and higher cancer-suppression efficiency. However, the efficacy of UNBS5162 in human retinoblastomas is still not clear. In the present study, we investigated the specific mechanism of UNBS5162 in the human retinoblastoma cell lines WERIRb1 and Y79. Compared with a negative-control (NC) group, UNBS5162 treatment for 72 hours significantly decreased cell proliferation; meanwhile, more apoptotic cells were observed in the UNBS5162-treated group (27.1% in WERIRb1, 20.83% in Y79) than in the NC group (11.59% in WERIRb1, 12.89% in Y79). We also found caspase 3 p17 and Bax expression to be upregulated and Bcl2 downregulated significantly in UNBS5162-treated WERIRb1 and Y79 cells. The effects of UNBS5162 on human retinoblastoma cells may be regulated by the Akt–mTOR pathway. We found expression of the Akt pathway and key proliferation-related genes – those for p-Akt, p-mTOR, p70, and cyclin D1 – were downregulated significantly in the UNBS5162-treated group compared with the NC group in WERIRb1 and Y79. Therefore, for the first time, we demonstrated that UNBS5162 can inhibit proliferation and promote apoptosis of human retinoblastoma cells by regulating activity of the Akt–mTOR pathway in vitro, suggesting the potential value of UNBS5162 in treatment for human retinoblastoma.

Keywords: UNBS5162, human retinoblastoma, cell apoptosis, WERIRb1, CXCL

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