Cancer Institute of Integrated Traditional Chinese and Western Medicine, Key Laboratory of Cancer Prevention and Therapy Combining Traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, Zhejiang 310012, China.
Department of Medical Oncology, Hangzhou, Zhejiang 310012, China.
Comb Chem High Throughput Screen. 2023;26(14):2517-2526. doi: 10.2174/1386207326666230320103437.
Sini decoction (SND) is a widely used Traditional Chinese Medicine (TCM). The reports of SND application in colorectal cancer (CRC) is limited.
The objective of this study is to investigate the anti-tumor activity of SND in the treatmeant of CRC.
SND was analyzed using high-performance liquid chromatography. A CRC metastasis model was established using murine CT-26 cells. Whole-body fluorescence imaging was used to observe CRC liver metastasis. Liver morphology was determined using hematoxylin-eosin staining. Cytokine mRNA expression (interleukin-2 (IL-2), interleukin-10 (IL-10), interferon-gamma (IFN-γ), and tumor necrosis factor beta (TNF-β)) were determined using real-time reverse transcription polymerase chain reaction. Spectral flow cytometry was used to detect mouse tumor immune subgroups. Databases were used to find potential target genes of SND. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used to identify potential signaling pathways of target genes.
SND suppressed CRC liver metastasis and alleviated liver injury . After SND treatment, IL-2 and IFN-γ were upregulated, whereas IL-10 and TGF-β were downregulated. Moreover, CD3+, CD8T cells, natural killer T cells, and macrophages increased significantly after SND treatment, while CD4CD25T cells decreased significantly. Importantly, increasing the aconite concentration had a better anti-tumor effect. Fifty-50 compounds in SND were screened, and 611 potential target genes were identified. Functional analyses showed that the genes were associated with the PI3K-Akt signaling pathway, EGFR tyrosine kinase inhibitor resistance, and HIF-1 signaling pathway.
SND exerts anti-tumor activity by inhibiting tumor progression and enhancing antitumor immunity in mice, suggesting its application to prevent and treat CRC.
四逆汤（SND）是一种广泛应用的中药。关于 SND 在结直肠癌（CRC）中的应用的报道有限。
本研究旨在探讨 SND 在 CRC 治疗中的抗肿瘤活性。
采用高效液相色谱法对 SND 进行分析。使用鼠 CT-26 细胞建立 CRC 转移模型。采用全身荧光成像观察 CRC 肝转移。采用苏木精-伊红染色观察肝形态。采用实时逆转录聚合酶链反应测定细胞因子 mRNA 表达（白细胞介素-2（IL-2）、白细胞介素-10（IL-10）、干扰素-γ（IFN-γ）和肿瘤坏死因子-β（TNF-β））。采用光谱流式细胞术检测小鼠肿瘤免疫亚群。利用数据库寻找 SND 的潜在靶基因。使用基因本体论和京都基因与基因组百科全书识别靶基因的潜在信号通路。
SND 抑制 CRC 肝转移并减轻肝损伤。SND 治疗后，IL-2 和 IFN-γ 上调，而 IL-10 和 TGF-β 下调。此外，SND 治疗后 CD3+、CD8+T 细胞、自然杀伤 T 细胞和巨噬细胞显著增加，而 CD4+CD25+T 细胞显著减少。重要的是，增加乌头浓度具有更好的抗肿瘤效果。从 SND 中筛选出 50 种化合物，鉴定出 611 个潜在靶基因。功能分析表明，这些基因与 PI3K-Akt 信号通路、EGFR 酪氨酸激酶抑制剂耐药性和 HIF-1 信号通路有关。
SND 通过抑制肿瘤进展和增强小鼠抗肿瘤免疫来发挥抗肿瘤活性，提示其在预防和治疗 CRC 中的应用。
