ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1588722
This article is part of the Research TopicThe Molecular Mechanisms and Therapeutic Implications of Protein Kinase Inhibitors in Cancer TherapyView all 6 articles
Dual PI3K/mTOR inhibitor NVP-BEZ235 induces cell cycle arrest via autophagy mediated protein degradation of RPL19 in Nephroblastoma cell
Provisionally accepted
- General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Region, China
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Nephroblastoma is the most common renal malignancy in children. NVP-BEZ235, a dual inhibitor of PI3K and mTOR, has demonstrated efficacy in inhibiting the growth of various cancers. However, the effects of NVP-BEZ235 on nephroblastoma therapy remain unclear. This study aimed to investigate the effects and mechnism of NVP-BEZ235 on nephroblastoma.The proliferation of G401 cells under NVP-BEZ235 treatment were evaluated by CCK-8, clone formation and EdU assay. The effect of NVP-BEZ235 on cell cycle was evaluated by western blot and flow cytometric analysis. To observe NVP-BEZ235's effect on autophagy, the proteins expression and autophagic flux were examined. The bioinformatic tools were used to evaluate the expression of RPL19 in tumor tissues.Furthermore, the interaction between autophagy and RPL19 were evaluated. The in vivo experiment was conducted to observe the effect of NVP-BEZ235 on tumor.NVP-BEZ235 was found to inhibit the proliferation of G401 cells. Then, we found that treatment of G401 cells with NVP-BEZ235 arrests the cell cycle in G2/M phase while inducing autophagy. Furthermore, RPL19 was overexpressed in nephroblastoma tissues. And NVP-BEZ235 suppressed the expression of RPL19 protein. In addition, NVP-BEZ235 was found to induce autophagy and thereby downregulate RPL19 expression in G401 cells. The in vivo study further confirmed that NVP-BEZ235 inhibited the growth of nephroblastoma. Induction of cell cycle arrest via autophagy-mediated protein degradation of RPL19 by dual PI3K/mTOR inhibitor NVP-BEZ235 effectively suppressed Nephroblastoma progression.
Keywords: NVP-BEZ235, PI3K, mTOR, rpL19, Autophagy
Received: 06 Mar 2025; Accepted: 04 Jul 2025.
Copyright: © 2025 Gao, Xing, Liu, Feng, Luo, Zhu and Su. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yongzhao Zhu, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Region, China
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