JQ1, a selective inhibitor of BRD4, suppresses retinoblastoma cell growth by inducing cell cycle arrest and apoptosis

Yanyan Zhang; Sujuan Duan; Alan Jang; Longbing Mao; Xing Liu; Guofu Huang

doi:10.1016/j.exer.2020.108304

JQ1, a selective inhibitor of BRD4, suppresses retinoblastoma cell growth by inducing cell cycle arrest and apoptosis

Exp Eye Res. 2021 Jan:202:108304. doi: 10.1016/j.exer.2020.108304. Epub 2020 Oct 17.

Authors

Yanyan Zhang¹, Sujuan Duan², Alan Jang³, Longbing Mao⁴, Xing Liu⁴, Guofu Huang⁵

Affiliations

¹ Department of Ophthalmology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China; Jiangxi Key Laboratory of Cancer Metastasis and Precision Treatment, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China; Medical Department of Graduate School, Nanchang University, Nanchang, Jiangxi, People's Republic of China.
² Department of Ophthalmology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China; Jiangxi Key Laboratory of Cancer Metastasis and Precision Treatment, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China.
³ Jiangxi Key Laboratory of Cancer Metastasis and Precision Treatment, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China.
⁴ Medical Department of Graduate School, Nanchang University, Nanchang, Jiangxi, People's Republic of China.
⁵ Department of Ophthalmology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China; Jiangxi Key Laboratory of Cancer Metastasis and Precision Treatment, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China. Electronic address: hgf2222@sina.com.

PMID: 33080301
DOI: 10.1016/j.exer.2020.108304

Abstract

Retinoblastoma (RB) is the most common intraocular cancer in children, and chemotherapy has been the first-line treatment. However, due to the side effects of chemotherapy drugs, novel treatments must be developed. JQ1, a selective inhibitor of BRD4, suppresses cell growth in several cancers in which BRD4 is overexpressed. In the present study, BRD4 was overexpressed in retinoblastoma, and JQ1 effectively inhibited RB cell proliferation and colony formation by inducing cell cycle arrest and promoting apoptosis. Furthermore, the Myc-P21-CDK2 and Myc-cyclinD3/CDK6 pathways were activated in RB cells treated with JQ1, and an animal experiment suggested that JQ1 significantly inhibited tumour growth in vivo. In conclusion, JQ1 may be a potential drug treatment for retinoblastoma.

Keywords: BRD4; JQ1; Retinoblastoma; WERI-Rb1; Y79.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Azepines / pharmacology*
Blotting, Western
Cell Cycle / drug effects*
Cell Cycle Proteins / antagonists & inhibitors*
Cell Cycle Proteins / genetics
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival
Gene Expression Regulation, Neoplastic / physiology
Humans
Immunohistochemistry
Male
Mice
Mice, Nude
RNA, Messenger / genetics
Real-Time Polymerase Chain Reaction
Retinal Neoplasms / genetics
Retinal Neoplasms / pathology*
Retinal Pigment Epithelium / drug effects
Retinoblastoma / genetics
Retinoblastoma / pathology*
Signal Transduction
Transcription Factors / antagonists & inhibitors*
Transcription Factors / genetics
Triazoles / pharmacology*

Substances

(+)-JQ1 compound
Antineoplastic Agents
Azepines
BRD4 protein, human
Cell Cycle Proteins
RNA, Messenger
Transcription Factors
Triazoles