PDF(Pubmed)
Abstract：
UNASSIGNED: Prostate cancer, marked by a high incidence and mortality rate, presents a significant challenge, especially in the context of castration-resistant prostate cancer (CRPC) with limited treatment options due to drug resistance. This study aims to explore the anti-tumor effects of Xihuang Pills (XHP) on CRPC, focusing on metabolic reprogramming and the Wnt/β-catenin pathway.
UNASSIGNED: In vitro and in vivo biofunctional assays were employed to assess the efficacy and mechanisms of XHP. Subcutaneous xenografts of PC3 in mice served as an in vivo model to evaluate XHP\'s anti-tumor activity. Tumor volume, weight, proliferation, and apoptosis were monitored. Various assays, including CCK8, TUNEL assay, QRT-PCR, and Western Blotting, were conducted to measure metabolic reprogramming, proliferation, apoptosis, and cell cycle in prostate cancer cells. RNA-seq analysis predicted XHP\'s impact on prostate cancer, validating the expression of Wnt/β-catenin-related proteins and mRNA. Additionally, 58 compounds in XHP were identified via LC-MS/MS, and molecular docking analysis connected these compounds to key genes.
UNASSIGNED: In vitro and in vivo experiments demonstrated that XHP significantly inhibited CRPC cell viability, induced apoptosis, and suppressed invasion and migration. mRNA sequencing revealed differentially expressed genes, with functional enrichment analysis indicating modulation of key biological processes. XHP treatment downregulated Wnt signaling pathway-related genes, including CCND2, PRKCG, and CCN4. Moreover, XHP effectively inhibited glucose uptake and lactate production, leading to reduced HIF-1α and glycolytic enzymes (GLUT1, HK2, PKM2), suggesting its potential in attenuating the Warburg effect. Molecular docking analysis suggested a plausible interaction between XHP\'s active compounds and Wnt1 protein, indicating a mechanism through which XHP modulates the Wnt/β-catenin pathway.
UNASSIGNED: XHP demonstrated remarkable efficacy in suppressing the growth, proliferation, apoptosis, migration, and invasiveness of prostate tumors. The interaction between XHP\'s active constituents and Wnt1 was evident, leading to the inhibition of Wnt1 and downstream anti-carcinogenic factors, thereby influencing the β-catenin/HIF-1α-mediated glycolysis.
UNASSIGNED: In vitro and in vivo biofunctional assays were employed to assess the efficacy and mechanisms of XHP. Subcutaneous xenografts of PC3 in mice served as an in vivo model to evaluate XHP\'s anti-tumor activity. Tumor volume, weight, proliferation, and apoptosis were monitored. Various assays, including CCK8, TUNEL assay, QRT-PCR, and Western Blotting, were conducted to measure metabolic reprogramming, proliferation, apoptosis, and cell cycle in prostate cancer cells. RNA-seq analysis predicted XHP\'s impact on prostate cancer, validating the expression of Wnt/β-catenin-related proteins and mRNA. Additionally, 58 compounds in XHP were identified via LC-MS/MS, and molecular docking analysis connected these compounds to key genes.
UNASSIGNED: In vitro and in vivo experiments demonstrated that XHP significantly inhibited CRPC cell viability, induced apoptosis, and suppressed invasion and migration. mRNA sequencing revealed differentially expressed genes, with functional enrichment analysis indicating modulation of key biological processes. XHP treatment downregulated Wnt signaling pathway-related genes, including CCND2, PRKCG, and CCN4. Moreover, XHP effectively inhibited glucose uptake and lactate production, leading to reduced HIF-1α and glycolytic enzymes (GLUT1, HK2, PKM2), suggesting its potential in attenuating the Warburg effect. Molecular docking analysis suggested a plausible interaction between XHP\'s active compounds and Wnt1 protein, indicating a mechanism through which XHP modulates the Wnt/β-catenin pathway.
UNASSIGNED: XHP demonstrated remarkable efficacy in suppressing the growth, proliferation, apoptosis, migration, and invasiveness of prostate tumors. The interaction between XHP\'s active constituents and Wnt1 was evident, leading to the inhibition of Wnt1 and downstream anti-carcinogenic factors, thereby influencing the β-catenin/HIF-1α-mediated glycolysis.
摘要：
■前列腺癌，以高发病率和高死亡率为标志，提出了一个重大挑战，特别是在去势抵抗性前列腺癌（CRPC）的背景下，由于耐药性，治疗选择有限。本研究旨在探讨西黄丸(XHP)对CRPC的抗肿瘤作用,重点关注代谢重编程和Wnt/β-catenin途径。
■采用体外和体内生物功能测定来评估XHP的功效和机制。PC3在小鼠体内的皮下异种移植物作为体内模型来评估XHP的抗肿瘤活性。肿瘤体积,体重,扩散,并监测细胞凋亡。各种化验，包括CCK8，TUNEL测定，QRT-PCR,和西方印迹，进行测量代谢重编程，扩散,凋亡，和前列腺癌细胞的细胞周期。RNA-seq分析预测XHP对前列腺癌的影响，验证Wnt/β-catenin相关蛋白和mRNA的表达。此外,XHP中58个化合物通过LC-MS/MS鉴定,分子对接分析将这些化合物与关键基因联系起来。
■体外和体内实验表明，XHP显著抑制CRPC细胞活力，诱导细胞凋亡，并抑制入侵和迁移。mRNA测序显示差异表达基因，功能富集分析表明调节关键的生物过程。XHP治疗下调Wnt信号通路相关基因,包括CCND2、PRKCG、CCN4。此外，XHP可有效抑制葡萄糖摄取和乳酸生成,导致HIF-1α和糖酵解酶（GLUT1，HK2，PKM2）减少，表明了它在减弱Warburg效应方面的潜力。分子对接分析表明XHP的活性化合物与Wnt1蛋白之间存在合理的相互作用，表明XHP调节Wnt/β-catenin途径的机制。
■XHP在抑制生长方面表现出显著的功效，扩散,凋亡，迁移,和前列腺肿瘤的侵袭性。XHP的活性成分与Wnt1之间的相互作用是明显的，导致Wnt1和下游抗癌因子的抑制，从而影响β-连环蛋白/HIF-1α介导的糖酵解。
■采用体外和体内生物功能测定来评估XHP的功效和机制。PC3在小鼠体内的皮下异种移植物作为体内模型来评估XHP的抗肿瘤活性。肿瘤体积,体重,扩散,并监测细胞凋亡。各种化验，包括CCK8，TUNEL测定，QRT-PCR,和西方印迹，进行测量代谢重编程，扩散,凋亡，和前列腺癌细胞的细胞周期。RNA-seq分析预测XHP对前列腺癌的影响，验证Wnt/β-catenin相关蛋白和mRNA的表达。此外,XHP中58个化合物通过LC-MS/MS鉴定,分子对接分析将这些化合物与关键基因联系起来。
■体外和体内实验表明，XHP显著抑制CRPC细胞活力，诱导细胞凋亡，并抑制入侵和迁移。mRNA测序显示差异表达基因，功能富集分析表明调节关键的生物过程。XHP治疗下调Wnt信号通路相关基因,包括CCND2、PRKCG、CCN4。此外，XHP可有效抑制葡萄糖摄取和乳酸生成,导致HIF-1α和糖酵解酶（GLUT1，HK2，PKM2）减少，表明了它在减弱Warburg效应方面的潜力。分子对接分析表明XHP的活性化合物与Wnt1蛋白之间存在合理的相互作用，表明XHP调节Wnt/β-catenin途径的机制。
■XHP在抑制生长方面表现出显著的功效，扩散,凋亡，迁移,和前列腺肿瘤的侵袭性。XHP的活性成分与Wnt1之间的相互作用是明显的，导致Wnt1和下游抗癌因子的抑制，从而影响β-连环蛋白/HIF-1α介导的糖酵解。
