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

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.

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC10901251 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature