Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China.
Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Aging (Albany NY). 2024 Mar 13;16(6):5387-5411. doi: 10.18632/aging.205654.
Prostate cancer (PCa) is a common malignancy in elderly men. We have applied Traditional Chinese Medicine CFF-1 in clinical treatments for PCa for several years. Here, we aimed to identify the underlying mechanism of CFF-1 on PCa using network pharmacology and experimental validation. Active ingredients, potential targets of CFF-1 were acquired from the public databases. Subsequently, protein-protein interaction (PPI) and the herbs-active ingredients-target network was constructed. A prognostic model for PCa was also constructed based on key targets. experiments using PCa cell lines CWR22Rv1 and PC-3 were carried out to validate the potential mechanism of CFF-1 on PCa. A total of 112 bioactive compounds and 359 key targets were screened from public databases. PPI and herbs-active ingredients-target network analysis determined 12 genes as the main targets of CFF-1 on PCa. Molecular docking studies indicated that the primary active ingredients of CFF-1 possess strong binding affinity to the top five hub targets. DNMT3B, RXRB and HPRT1 were found to be involved in immune regulation of PCa. , CFF-1 was found to inhibit PCa cell proliferation, migration, invasion and induce apoptosis via PI3K-Akt, HIF-1, TNF, EGFR-TKI resistance and PD-1 checkpoint signaling pathways. This study comprehensively elucidates the underlying molecular mechanism of CFF-1 against PCa, offering a strong rationale for clinical application of CFF-1 in PCa treatment.
前列腺癌（PCa）是老年男性常见的恶性肿瘤。我们已经将中药 CFF-1 应用于 PCa 的临床治疗多年。在这里，我们旨在通过网络药理学和实验验证来确定 CFF-1 对 PCa 的潜在作用机制。从公共数据库中获取 CFF-1 的活性成分和潜在靶标。随后，构建了蛋白质-蛋白质相互作用（PPI）和草药-活性成分-靶标网络。还根据关键靶标构建了 PCa 的预后模型。使用 PCa 细胞系 CWR22Rv1 和 PC-3 进行实验，验证 CFF-1 对 PCa 的潜在作用机制。从公共数据库中筛选出 112 种生物活性化合物和 359 个关键靶标。PPI 和草药-活性成分-靶标网络分析确定了 12 个基因作为 CFF-1 对 PCa 的主要靶标。分子对接研究表明，CFF-1 的主要活性成分与前五个枢纽靶标具有很强的结合亲和力。DNMT3B、RXRB 和 HPRT1 被发现参与了 PCa 的免疫调节。研究表明，CFF-1 通过 PI3K-Akt、HIF-1、TNF、EGFR-TKI 耐药和 PD-1 检查点信号通路抑制 PCa 细胞增殖、迁移、侵袭并诱导细胞凋亡。本研究全面阐明了 CFF-1 对抗 PCa 的潜在分子机制，为 CFF-1 在 PCa 治疗中的临床应用提供了强有力的依据。
