由于药物治疗有限，治疗无功能垂体腺瘤 (NFPA) 很困难。卡麦角林 (CAB) 对 NFPA 的有效性存在争议。本研究探讨了 HTR2B 在 NFPA 中的作用及其治疗潜力。我们对大量 RNA 测序数据进行了筛选，以分析 NFPA 样本中的 HTR2B 表达水平。进行体外和体内实验来评估 HTR2B 调节对肿瘤生长和细胞周期调节的影响。使用药理学抑制剂和分子相互作用测定阐明了 HTR2B 介导的信号通路的机制。在 NFPA 样本中检测到 HTR2B 表达升高，这与肿瘤存活率增加相关。抑制 HTR2B 活性可通过调节 G2M 细胞周期抑制肿瘤生长。研究发现，PRX-08066 对 HTR2B 的抑制可通过干扰 Gαq/PLC/PKC 途径来阻断 STAT3 磷酸化和核转位。 PKC-γ 和 STAT3 之间的直接相互作用对于 STAT3 激活至关重要。 CAB 被证明可以通过 HTR2B 激活 pSTAT3，从而降低其治疗潜力。然而，HTR2B 拮抗剂与 CAB 的组合显着抑制了表达 HTR2B 的垂体肿瘤细胞系、异种移植垂体肿瘤模型和患者来源的样品中的肿瘤细胞增殖。对患者数据的分析表明，以 HTR2B/PKC-γ 上调和 BTG2/GADD45A 下调为特征的独特分子模式可能受益于 CAB 和 PRX-08066 的联合治疗。HTR2B 是 NFPA 的潜在治疗靶点，其抑制可能提高 CAB 疗效。双重治疗方法可能对 HTR2B 高表达的 NFPA 患者有益。© 作者 2024。由牛津大学出版社代表神经肿瘤学会出版。版权所有。如需商业重复使用，请联系 reprints@oup.com 获取转载和转载的翻译权。所有其他权限均可通过我们网站文章页面上的“权限”链接通过我们的 RightsLink 服务获得 - 如需了解更多信息，请联系journals.permissions@oup.com。

Managing non-functioning pituitary adenomas (NFPAs) is difficult due to limited drug treatments. Cabergoline's (CAB) effectiveness for NFPAs is debated. This study explores the role of HTR2B in NFPAs and its therapeutic potential.We conducted screening of bulk RNA-sequencing data to analyze HTR2B expression levels in NFPA samples. In vitro and in vivo experiments were performed to evaluate the effects of HTR2B modulation on tumor growth and cell cycle regulation. Mechanistic insights into the HTR2B-mediated signaling pathway were elucidated using pharmacological inhibitors and molecular interaction assays.Elevated HTR2B expression was detected in NFPA samples, which was associated with increased tumor survival. Inhibition of HTR2B activity resulted in the suppression of tumor growth through modulation of the G2M cell cycle. The inhibition of HTR2B with PRX-08066 was found to block STAT3 phosphorylation and nuclear translocation by interfering with the Gαq/PLC/PKC pathway. A direct interaction between PKC-γ and STAT3 was critical for STAT3 activation. CAB was shown to activate pSTAT3 via HTR2B, reducing its therapeutic potential. However, the combination of an HTR2B antagonist with CAB significantly inhibited tumor cell proliferation in HTR2B-expressing pituitary tumor cell lines, a xenografted pituitary tumor model, and patient-derived samples. Analysis of patient-derived data indicated that a distinct molecular pattern characterized by upregulated HTR2B/PKC-γ and downregulated BTG2/GADD45A may benefit from combination treatment with CAB and PRX-08066.HTR2B is a potential therapeutic target for NFPAs, and its inhibition could improve CAB efficacy. A dual therapy approach may be beneficial for NFPA patients with high HTR2B expression.© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.