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.
Yanyan Zhang  1 ,  Sujuan Duan  2 ,  Alan Jang  3 ,  Longbing Mao  4 ,  Xing Liu  4 ,  Guofu Huang  5
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: [email protected].
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.
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