Prostate cancer (PCa) depends on androgen receptor (AR) signaling to regulate cell metabolism, including glycolysis, and thereby promotes tumor growth. Glycolysis is overactive in PCa and associated with poor prognosis, but the therapeutic efficacy of glycolysis inhibitors has thus far been limited by their inability to induce cell death. FV-429, a flavonoid derivative of Wogonin, is a glycolysis inhibitor that has shown anti-cancer promise. In this study, we used FV-429 as an anti-PCa agent and investigated its mechanisms of action. In vitro, both the glycolytic ability and the viability of PCa cells were inhibited by FV-429. We found that FV-429 could induce mitochondrial dysfunction and apoptosis, with AKT-HK2 signaling pathway playing a key role. In addition, FV-429 had a pro-apoptotic effect on human prostate cancer cells that relied on the inhibition of AR expression and activity. In vivo, FV-429 exerted significant tumor-repressing activity with high safety in the xenograft model using LNCaP cells. In summary, we demonstrated that FV-429 induced glycolysis inhibition and apoptosis in human prostate cancer cells by downregulating the AR-AKT-HK2 signaling network, making FV-429 a promising candidate as one therapeutic agent for advanced PCa.

前列腺癌（PCa）依赖于雄激素受体（AR）信号来调节细胞代谢（包括糖酵解），从而促进肿瘤生长。糖酵解在PCa中过度活跃，并与不良预后相关，但迄今为止，糖酵解抑制剂的治疗功效因无法诱导细胞死亡而受到限制。FV-429是Wogonin的类黄酮衍生物，是一种糖酵解抑制剂，具有抗癌作用。在这项研究中，我们使用FV-429作为抗PCa药物并研究了其作用机理。体外FV-429抑制PCa细胞的糖酵解能力和生存能力。我们发现FV-429可以诱导线粒体功能障碍和细胞凋亡，其中AKT-HK2信号通路起关键作用。此外，FV-429对人类前列腺癌细胞具有促凋亡作用，这依赖于对AR表达和活性的抑制。在体内，FV-429在使用LNCaP细胞的异种移植模型中具有显着的肿瘤抑制活性，具有很高的安全性。总之，我们证明了FV-429通过下调AR-AKT-HK2信号网络诱导人前列腺癌细胞中的糖酵解抑制和细胞凋亡，使FV-429成为一种有前途的候选药物作为晚期PCa的治疗药物。