组蛋白去甲基化酶抑制剂 GSK-J4 在视网膜母细胞瘤中的抗肿瘤潜力。
Antitumoral Potential of the Histone Demethylase Inhibitor GSK-J4 in Retinoblastoma.
机构信息
Department of Ophthalmology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, PR China.
Medical Department of Graduate School, Nanchang University, Nanchang, Jiangxi, PR China.
出版信息
Invest Ophthalmol Vis Sci. 2024 Feb 1;65(2):34. doi: 10.1167/iovs.65.2.34.
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.
目的
本研究旨在探讨 GSK-J4 对视网膜母细胞瘤的抗肿瘤作用及其相关的生物学功能和分子机制。
方法
通过体外和体内实验评估 GSK-J4 对视网膜母细胞瘤的抗肿瘤作用。通过 CCK-8、EdU 掺入和软琼脂集落形成实验来检测 GSK-J4 对细胞增殖的影响。通过流式细胞术评估 GSK-J4 对细胞周期和凋亡的影响。通过 RNA-seq 和 Western blot 来探讨 GSK-J4 的分子机制。建立原位异种移植模型来确定 GSK-J4 对肿瘤生长的影响。
结果
GSK-J4 显著抑制视网膜母细胞瘤细胞在体外和体内的增殖，将细胞周期阻滞在 G2/M 期，并诱导细胞凋亡。在机制上，GSK-J4 可能通过调节 PI3K/AKT/NF-κB 信号通路来抑制视网膜母细胞瘤细胞的生长。
结论
GSK-J4 对视网膜母细胞瘤具有显著的抗肿瘤作用，至少部分是通过抑制 PI3K/AKT/NF-κB 通路介导的。本研究为视网膜母细胞瘤的治疗提供了一种新的策略。
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