2. Academic Validation
  3. Antitumoral Potential of the Histone Demethylase Inhibitor GSK-J4 in Retinoblastoma

Antitumoral Potential of the Histone Demethylase Inhibitor GSK-J4 in Retinoblastoma

  • Invest Ophthalmol Vis Sci. 2024 Feb 1;65(2):34. doi: 10.1167/iovs.65.2.34.
Yanyan Zhang 1 2 3,  Weiqi Wu 1 2 3,  Caixia Xu 1 2,  Hongwei Yang 1 2,  Guofu Huang 1 3 4
Affiliations

Affiliations

  • 1 Department of Ophthalmology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, PR China.
  • 2 Medical Department of Graduate School, Nanchang University, Nanchang, Jiangxi, PR China.
  • 3 Jiangxi Provincial Key Laboratory of Tumor Metastasis and Precision Therapy, Center Laboratory, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, PR China.
  • 4 Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, Guangdong, PR China.
PMID: 38393716 DOI: 10.1167/iovs.65.2.34
Abstract

Purpose: The purpose of this study was to investigate the antitumor effects of GSK-J4 on retinoblastoma, as well as its related biological functions and molecular mechanisms.

Methods: The antitumor effect of GSK-J4 on retinoblastoma was evaluated by in vitro and in vivo assays. CCK-8, EdU incorporation, and soft agar colony formation assays were performed to examine the effect of GSK-J4 on cell proliferation. Flow cytometry was used to evaluate the effect of GSK-J4 on the cell cycle and Apoptosis. RNA-seq and Western blotting were conducted to explore the molecular mechanisms of GSK-J4. An orthotopic xenograft model was established to determine the effect of GSK-J4 on tumor growth.

Results: GSK-J4 significantly inhibited retinoblastoma cell proliferation both in vitro and in vivo, arrested the cell cycle at G2/M phase, and induced Apoptosis. Mechanistically, GSK-J4 may suppress retinoblastoma cell growth by regulating the PI3K/Akt/NF-κB signaling pathway.

Conclusions: The antitumor effects of GSK-J4 were noticeable in retinoblastoma and were at least partially mediated by PI3K/Akt/NF-κB pathway suppression. Our study provides a novel strategy for the treatment of retinoblastoma.

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