Sini Decoction Inhibits Tumor Progression and Enhances the Anti-Tumor Immune Response in a Murine Model of Colon Cancer

Jiabin Chen; Xiaoxiao Zheng; Guoshu Xu; Baoming Wang; Liqiang Hu; Jiayan Mao; Xuemei Lu; Ying Cai; Kequn Chai; Wei Chen

doi:10.2174/1386207326666230320103437

Sini Decoction Inhibits Tumor Progression and Enhances the Anti-Tumor Immune Response in a Murine Model of Colon Cancer

Comb Chem High Throughput Screen. 2023;26(14):2517-2526. doi: 10.2174/1386207326666230320103437.

Authors

Jiabin Chen^{1

2

3}, Xiaoxiao Zheng^{1

4

3}, Guoshu Xu^{1

4}, Baoming Wang^{1

4}, Liqiang Hu^{1

4}, Jiayan Mao^{1

4}, Xuemei Lu^{1

4}, Ying Cai^{1

4}, Kequn Chai^{1

4}, Wei Chen^{1

4

3}

Affiliations

¹ 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.
² Department of Medical Oncology, Hangzhou, Zhejiang 310012, China.
³ Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310051, China.
⁴ Department of Medical Oncology, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, China.

PMID: 36959128
DOI: 10.2174/1386207326666230320103437

Abstract

Background: Sini decoction (SND) is a widely used Traditional Chinese Medicine (TCM). The reports of SND application in colorectal cancer (CRC) is limited.

Objective: The objective of this study is to investigate the anti-tumor activity of SND in the treatmeant of CRC.

Methods: 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.

Results: SND suppressed CRC liver metastasis and alleviated liver injury in vivo. After SND treatment, IL-2 and IFN-γ were upregulated, whereas IL-10 and TGF-β were downregulated. Moreover, CD3+, CD8⁺T cells, natural killer T cells, and macrophages increased significantly after SND treatment, while CD4⁺CD25⁺T 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.

Conclusion: SND exerts anti-tumor activity by inhibiting tumor progression and enhancing antitumor immunity in mice, suggesting its application to prevent and treat CRC.

Keywords: Colon cancer; PI3K-Akt signaling pathway; immune response; network pharmacology; sini decoction; tumor microenvironment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Colonic Neoplasms* / drug therapy
Disease Models, Animal
Immunity
Interleukin-10
Interleukin-2
Liver Neoplasms* / drug therapy
Mice
Phosphatidylinositol 3-Kinases

Substances

sini tang
Interleukin-2
Interleukin-10
Phosphatidylinositol 3-Kinases