Abstract：
BACKGROUND: Fuzheng Xiaozheng prescription (FZXZP), a traditional Chinese medicine, which was derived from the famous decoction, Sanjiasan, in the book of \"Wenyilun\" in Ming dynasty. Due to its function of invigorating the circulation of blood in Chinese medicine, it was usually used for treating the liver cirrhosis, hepatocellular carcinoma (HCC), etc. Clinical application found that FZXZP exhibited satisfactory therapeutic effects in HCC treatments. However, we still know little about the underlying mechanisms.
OBJECTIVE: In this study, we aim to gain a deeper insight into the inhibiting effects of FZXZP on HCC rats and preliminarily elucidate the underlying intervention effects.
METHODS: Two doses of FZXZP were adopted to evaluate the therapeutic effects on rat HCC, and then the intervention effects were evaluated from different aspects. High performance liquid chromatography (HPLC) was used for the active compounds prediction in FZXZP. Finally, the mRNA-Seq was conducted to reveal the intervention mechanisms and the mechanisms were further validated by quantitative Real-time PCR (qRT-PCR) and lipid contents analyses.
RESULTS: The results showed that FZXZP significantly alleviated the serum biochemical indicators and improved the pathological characteristics of HCC rats. Mechanistically, FZXZP could regulate some lipid related metabolisms, including arachidonic acid, linoleic acid and retinol, as well as improving the steroid hormone biosynthesis, to improve the inflammatory statuses and restoring ability of HCC livers, and these were further confirmed by our following analyses on serum lipid contents and cytokine expressions. In addition, FZXZP could also negatively regulate four extracellular growth factors which could result in the blocking of two cancer-related signaling pathways, Ras/MAPK and Ras/PI3K-Akt.
CONCLUSIONS: Our results suggested that FZXZP demonstrated significant inhibiting effects on rat HCC progresses, and these may be realized by improving the inflammatory statuses and blocking the Ras/MAPK and Ras/PI3K-Akt signaling pathways.
OBJECTIVE: In this study, we aim to gain a deeper insight into the inhibiting effects of FZXZP on HCC rats and preliminarily elucidate the underlying intervention effects.
METHODS: Two doses of FZXZP were adopted to evaluate the therapeutic effects on rat HCC, and then the intervention effects were evaluated from different aspects. High performance liquid chromatography (HPLC) was used for the active compounds prediction in FZXZP. Finally, the mRNA-Seq was conducted to reveal the intervention mechanisms and the mechanisms were further validated by quantitative Real-time PCR (qRT-PCR) and lipid contents analyses.
RESULTS: The results showed that FZXZP significantly alleviated the serum biochemical indicators and improved the pathological characteristics of HCC rats. Mechanistically, FZXZP could regulate some lipid related metabolisms, including arachidonic acid, linoleic acid and retinol, as well as improving the steroid hormone biosynthesis, to improve the inflammatory statuses and restoring ability of HCC livers, and these were further confirmed by our following analyses on serum lipid contents and cytokine expressions. In addition, FZXZP could also negatively regulate four extracellular growth factors which could result in the blocking of two cancer-related signaling pathways, Ras/MAPK and Ras/PI3K-Akt.
CONCLUSIONS: Our results suggested that FZXZP demonstrated significant inhibiting effects on rat HCC progresses, and these may be realized by improving the inflammatory statuses and blocking the Ras/MAPK and Ras/PI3K-Akt signaling pathways.
摘要：
背景：扶正消症处方（FZXZP），中药，它来自著名的汤剂，三甲三,在明代的“文义伦”书中。由于其在中药中具有活血化瘀的作用,它通常用于治疗肝硬化，肝细胞癌（HCC），等。临床应用发现，FZXZP在HCC治疗中表现出满意的治疗效果。然而,我们仍然对潜在的机制知之甚少。
目的：在本研究中，我们旨在更深入地了解FZXZP对HCC大鼠的抑制作用，并初步阐明潜在的干预作用。
方法：采用两种剂量的FZXZP来评估对大鼠HCC的治疗效果。从不同方面评价干预效果。高效液相色谱法(HPLC)用于FZXZP中活性化合物的预测。最后,通过mRNA-Seq揭示干预机制,并通过实时定量PCR(qRT-PCR)和脂质含量分析进一步验证机制.
结果：结果表明，FZXZP可明显缓解HCC大鼠的血清生化指标，改善其病理特征。机械上,FZXZP可以调节某些脂质相关代谢，包括花生四烯酸,亚油酸和视黄醇，以及改善类固醇激素的生物合成，改善肝细胞癌肝脏的炎症状态和恢复能力，我们对血清脂质含量和细胞因子表达的分析进一步证实了这一点。此外,FZXZP还可以负调节四种细胞外生长因子，这可能导致两种癌症相关信号通路的阻断，Ras/MAPK和Ras/PI3K-Akt.
结论：我们的结果表明，FZXZP对大鼠肝癌进展具有显著的抑制作用，这些可能通过改善炎症状态和阻断Ras/MAPK和Ras/PI3K-Akt信号通路来实现。
目的：在本研究中，我们旨在更深入地了解FZXZP对HCC大鼠的抑制作用，并初步阐明潜在的干预作用。
方法：采用两种剂量的FZXZP来评估对大鼠HCC的治疗效果。从不同方面评价干预效果。高效液相色谱法(HPLC)用于FZXZP中活性化合物的预测。最后,通过mRNA-Seq揭示干预机制,并通过实时定量PCR(qRT-PCR)和脂质含量分析进一步验证机制.
结果：结果表明，FZXZP可明显缓解HCC大鼠的血清生化指标，改善其病理特征。机械上,FZXZP可以调节某些脂质相关代谢，包括花生四烯酸,亚油酸和视黄醇，以及改善类固醇激素的生物合成，改善肝细胞癌肝脏的炎症状态和恢复能力，我们对血清脂质含量和细胞因子表达的分析进一步证实了这一点。此外,FZXZP还可以负调节四种细胞外生长因子，这可能导致两种癌症相关信号通路的阻断，Ras/MAPK和Ras/PI3K-Akt.
结论：我们的结果表明，FZXZP对大鼠肝癌进展具有显著的抑制作用，这些可能通过改善炎症状态和阻断Ras/MAPK和Ras/PI3K-Akt信号通路来实现。
