Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
Department of Infectious Diseases, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing, China.
Phytomedicine. 2021 Jul;87:153575. doi: 10.1016/j.phymed.2021.153575. Epub 2021 Apr 18.
Hepatocellular carcinoma (HCC) is a common malignant tumor with limited treatment options. Conventional antitumor therapy combined with traditional Chinese medicine (TCM) to limit tumor progression has gradually become the focus of complementary and alternative therapies for HCC treatment. The Fuzheng Jiedu Xiaoji formulation (FZJDXJ) alleviates the clinical symptoms of patients and inhibits tumor progression, but its curative effect still requires extensive clinical research and mechanistic analysis.
To explore the effectiveness of FZJDXJ in HCC patients and investigate its biological function and mechanism underlying anticancer therapy.
This randomized controlled clinical trial enrolled 291 HCC patients receiving transcatheter arterial chemoembolization (TACE) therapy; patients received either FZJDXJ combined with standard treatment, or standard treatment alone, for 48 weeks. Statistical analyses were performed according to survival time at the end of the trial. The main constituents of the FZJDXJ extracts were identified and evaluated using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and molecular docking. The antitumor effects of FZJDXJ and its specific biological mechanism of action were studied.
After 48 weeks of treatment, one-year overall survival (OS) and progression-free survival (PFS) were significantly different between the two groups. Co-administration of FZJDXJ and TACE prolonged the OS of HCC patients, especially in BCLC A or B stage. FZJDXJ and TACE treatment effectively extended the PFS of patients, especially in the BCLC B stage. HPLC-MS/MS identified 1619 active constituents of FZJDXJ, including formononetin, chlorogenic acid (CGA), caffeic acid, luteolin, gallic acid, diosgenin, ergosterol endoperoxide, and lupeol, which may function through the AKT/CyclinD1/p21/p27 pathways. Through molecular docking, CGA and gallic acid could effectively combine with Thr308, an important phosphorylation site of AKT1. FZJDXJ inhibited tumor growth in nude mice. In vitro, FZJDXJ-mediated serum inhibited the proliferation, migration, and invasion of liver cancer cells, and promoted cell apoptosis.
Clinically, FZJDXJ combined with TACE therapy significantly prolonged OS and PFS and reduced the mortality rate of HCC patients. Mechanistically, FZJDXJ effectively inhibited the proliferation and migration of liver cancer cells through the modulation of the AKT/CyclinD1/p21/p27 pathways, and may be a promising TCM drug for anti-HCC therapy.
肝细胞癌（HCC）是一种常见的恶性肿瘤，治疗选择有限。常规抗肿瘤治疗联合中药（TCM）限制肿瘤进展，逐渐成为 HCC 治疗的补充和替代疗法的焦点。扶正解毒消积方（FZJDXJ）缓解患者临床症状，抑制肿瘤进展，但疗效仍需广泛的临床研究和机制分析。
探讨 FZJDXJ 对 HCC 患者的疗效，并探讨其抗癌治疗的生物学功能和机制。
这项随机对照临床试验纳入了 291 名接受经导管动脉化疗栓塞术（TACE）治疗的 HCC 患者；患者接受 FZJDXJ 联合标准治疗或单独标准治疗 48 周。根据试验结束时的生存时间进行统计分析。采用高效液相色谱-串联质谱（HPLC-MS/MS）和分子对接法鉴定和评价 FZJDXJ 提取物的主要成分。研究了 FZJDXJ 的抗肿瘤作用及其特定的生物学作用机制。
治疗 48 周后，两组患者的 1 年总生存率（OS）和无进展生存率（PFS）有显著差异。FZJDXJ 联合 TACE 可延长 HCC 患者的 OS，特别是在 BCLC A 或 B 期。FZJDXJ 和 TACE 治疗可有效延长患者的 PFS，特别是在 BCLC B 期。HPLC-MS/MS 鉴定出 FZJDXJ 的 1619 种活性成分，包括芒柄花素、绿原酸（CGA）、咖啡酸、木樨草素、没食子酸、薯蓣皂苷元、麦角甾醇过氧化物和羽扇豆醇，这些成分可能通过 AKT/CyclinD1/p21/p27 通路发挥作用。通过分子对接，CGA 和没食子酸可有效与 AKT1 的重要磷酸化位点 Thr308 结合。FZJDXJ 抑制裸鼠肿瘤生长。体外，FZJDXJ 介导的血清可抑制肝癌细胞的增殖、迁移和侵袭，并促进细胞凋亡。
临床研究表明，FZJDXJ 联合 TACE 治疗可显著延长 HCC 患者的 OS 和 PFS，并降低死亡率。机制上，FZJDXJ 通过调节 AKT/CyclinD1/p21/p27 通路有效抑制肝癌细胞的增殖和迁移，可能是一种有前途的抗 HCC 中药药物。
