Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

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

Author(s): Jiabin Chen, Xiaoxiao Zheng, Guoshu Xu, Baoming Wang, Liqiang Hu, Jiayan Mao, Xuemei Lu, Ying Cai, Kequn Chai* and Wei Chen*

Volume 26, Issue 14, 2023

Published on: 28 April, 2023

Page: [2517 - 2526] Pages: 10

DOI: 10.2174/1386207326666230320103437

Price: $65

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.

[1]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2019. CA Cancer J. Clin., 2019, 69(1), 7-34.
[http://dx.doi.org/10.3322/caac.21551] [PMID: 30620402]
[2]
Brenner, H.; Kloor, M.; Pox, C.P. Colorectal cancer. Lancet, 2014, 383(9927), 1490-1502.
[http://dx.doi.org/10.1016/S0140-6736(13)61649-9] [PMID: 24225001]
[3]
Faugeras, L.; Dili, A.; Druez, A.; Krug, B.; Decoster, C.; D’Hondt, L. Treatment options for metastatic colorectal cancer in patients with liver dysfunction due to malignancy. Crit. Rev. Oncol. Hematol., 2017, 115, 59-66.
[http://dx.doi.org/10.1016/j.critrevonc.2017.03.029] [PMID: 28602170]
[4]
Chen, Q.; Liu, J.; Wang, W.; Liu, S.; Yang, X.; Chen, M.; Cheng, L.; Lu, J.; Guo, T.; Huang, F. Sini decoction ameliorates sepsis-induced acute lung injury via regulating ACE2-Ang (1-7)-Mas axis and inhibiting the MAPK signaling pathway. Biomed. Pharmacother., 2019, 115, 108971.
[http://dx.doi.org/10.1016/j.biopha.2019.108971] [PMID: 31102910]
[5]
Brislinger, D.; Daxböck, C.; Roßmanith, E.; Stückler, M.; Lang, I.; Falkenhagen, D. Bai Hu Tang, Si Ni Tang, and Xue Bi Tang amplify pro-inflammatory activities and reduce apoptosis in endothelial cells in a cell culture model of sepsis. J. Ethnopharmacol., 2018, 225, 309-318.
[http://dx.doi.org/10.1016/j.jep.2018.07.021] [PMID: 30036577]
[6]
Lai, F.; Zhou, G.; Mai, S.; Qin, X.; Liu, W.; Zhang, Y.; Xie, D.; Weng, Y.; Du, J.; Zheng, Y.; Liao, J.; Han, Y. Sini decoction improves adrenal function and the short-term outcome of septic rats through downregulation of adrenal toll-like receptor 4 expression. Evid. Based Complement. Alternat. Med., 2018, 2018, 1-9.
[http://dx.doi.org/10.1155/2018/5186158] [PMID: 30018657]
[7]
Zhou, J.; Ma, X.; Shi, M.; Chen, C.; Sun, Y.; Li, J.; Xiong, Y.; Chen, J.; Li, F. Serum metabolomics analysis reveals that obvious cardioprotective effects of low dose Sini decoction against isoproterenol-induced myocardial injury in rats. Phytomedicine, 2017, 31, 18-31.
[http://dx.doi.org/10.1016/j.phymed.2017.01.009] [PMID: 28606513]
[8]
Tan, G.; Lou, Z.; Liao, W.; Dong, X.; Zhu, Z.; Li, W.; Chai, Y. Hydrophilic interaction and reversed-phase ultraperformance liquid chromatographyTOF-MS for serum metabonomic analysis of myocardial infarction in rats and its applications. Mol. Biosyst., 2012, 8(2), 548-556.
[http://dx.doi.org/10.1039/C1MB05324H] [PMID: 22037674]
[9]
Livak, K.J.; Schmittgen, T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)). Method. Methods, 2001, 25(4), 402-408.
[http://dx.doi.org/10.1006/meth.2001.1262] [PMID: 11846609]
[10]
Pretzsch, E.; Bösch, F.; Neumann, J.; Ganschow, P.; Bazhin, A.; Guba, M.; Werner, J.; Angele, M. Mechanisms of metastasis in colorectal cancer and metastatic organotropism: Hematogenous versus peritoneal spread. J. Oncol., 2019, 2019, 7407190.
[http://dx.doi.org/10.1155/2019/7407190] [PMID: 31641356]
[11]
Tan, Z.; Xue, H.; Sun, Y.; Zhang, C.; Song, Y.; Qi, Y. The role of tumor inflammatory microenvironment in lung cancer. Front. Pharmacol., 2021, 12, 688625.
[http://dx.doi.org/10.3389/fphar.2021.688625] [PMID: 34079469]
[12]
Goubran, H.A.; Kotb, R.R.; Stakiw, J.; Emara, M.E.; Burnouf, T. Regulation of tumor growth and metastasis: the role of tumor microenvironment. Cancer Growth Metastasis, 2014, 7, CGM.S11285.
[http://dx.doi.org/10.4137/CGM.S11285] [PMID: 24926201]
[13]
Jia, W.; Wang, L. Using traditional chinese medicine to treat hepatocellular carcinoma by targeting tumor immunity. Evid. Based Complement. Alternat. Med., 2020, 2020, 9843486.
[http://dx.doi.org/10.1155/2020/9843486] [PMID: 32595757]
[14]
Huang, H.; Fang, J.; Fan, X.; Miyata, T.; Hu, X.; Zhang, L.; Zhang, L.; Cui, Y.; Liu, Z.; Wu, X. Advances in molecular mechanisms for traditional chinese medicine actions in regulating tumor immune responses. Front. Pharmacol., 2020, 11, 1009.
[http://dx.doi.org/10.3389/fphar.2020.01009] [PMID: 32733246]
[15]
Mao, D.; Feng, L.; Gong, H. The antitumor and immunomodulatory effect of yanghe decoction in breast cancer is related to the modulation of the JAK/STAT signaling pathway. Evid. Based Complement. Alternat. Med., 2018, 2018, 8460526.
[http://dx.doi.org/10.1155/2018/8460526] [PMID: 30581487]
[16]
Pagès, F.; Berger, A.; Camus, M.; Sanchez-Cabo, F.; Costes, A.; Molidor, R.; Mlecnik, B.; Kirilovsky, A.; Nilsson, M.; Damotte, D.; Meatchi, T.; Bruneval, P.; Cugnenc, P.H.; Trajanoski, Z.; Fridman, W.H.; Galon, J. Effector memory T cells, early metastasis, and survival in colorectal cancer. N. Engl. J. Med., 2005, 353(25), 2654-2666.
[http://dx.doi.org/10.1056/NEJMoa051424] [PMID: 16371631]
[17]
Ihara, F.; Sakurai, D.; Takami, M.; Kamata, T.; Kunii, N.; Yamasaki, K.; Iinuma, T.; Nakayama, T.; Motohashi, S.; Okamoto, Y. Regulatory T cells induce CD4− NKT cell anergy and suppress NKT cell cytotoxic function. Cancer Immunol. Immunother., 2019, 68(12), 1935-1947.
[http://dx.doi.org/10.1007/s00262-019-02417-6] [PMID: 31641795]
[18]
Liu, C.; Yao, Z.; Wang, J.; Zhang, W.; Yang, Y.; Zhang, Y.; Qu, X.; Zhu, Y.; Zou, J.; Peng, S.; Zhao, Y.; Zhao, S.; He, B.; Mi, Q.; Liu, X.; Zhang, X.; Du, Q. Macrophage-derived CCL5 facilitates immune escape of colorectal cancer cells via the p65/STAT3-CSN5-PD-L1 pathway. Cell Death Differ., 2020, 27(6), 1765-1781.
[http://dx.doi.org/10.1038/s41418-019-0460-0] [PMID: 31802034]
[19]
Zhao, S.; Mi, Y.; Guan, B.; Zheng, B.; Wei, P.; Gu, Y.; Zhang, Z.; Cai, S.; Xu, Y.; Li, X.; He, X.; Zhong, X.; Li, G.; Chen, Z.; Li, D. Tumor-derived exosomal miR-934 induces macrophage M2 polarization to promote liver metastasis of colorectal cancer. J. Hematol. Oncol., 2020, 13(1), 156.
[http://dx.doi.org/10.1186/s13045-020-00991-2] [PMID: 33213490]
[20]
Cheng, H.; Wang, Z.; Fu, L.; Xu, T. Macrophage polarization in the development and progression of ovarian cancers: An overview. Front. Oncol., 2019, 9, 421.
[http://dx.doi.org/10.3389/fonc.2019.00421] [PMID: 31192126]
[21]
Badawi, M.A.; Abouelfadl, D.M.; El-Sharkawy, S.L.; Abd El-Aal, W.E.; Abbas, N.F. Tumor-associated macrophage (TAM) and angiogenesis in human colon carcinoma. Open Access Maced. J. Med. Sci., 2015, 3(2), 209-214.
[http://dx.doi.org/10.3889/oamjms.2015.044] [PMID: 27275223]
[22]
Wang, H.; Tian, T.; Zhang, J. Tumor-associated macrophages (TAMs) in colorectal cancer (CRC): From mechanism to therapy and prognosis. Int. J. Mol. Sci., 2021, 22(16), 8470.
[http://dx.doi.org/10.3390/ijms22168470] [PMID: 34445193]
[23]
Jedinak, A.; Dudhgaonkar, S.; Sliva, D. Activated macrophages induce metastatic behavior of colon cancer cells. Immunobiology, 2010, 215(3), 242-249.
[http://dx.doi.org/10.1016/j.imbio.2009.03.004] [PMID: 19457576]
[24]
Chen, M.; Hu, C.; Gao, Q.; Li, L.; Cheng, Z.; Li, Q.; Li, Z.; Wang, Z.; Mao, Z.; Tian, W.; Zhang, X. Study on metastasis inhibition of Kejinyan decoction on lung cancer by affecting tumor microenvironment. Cancer Cell Int., 2020, 20(1), 451.
[http://dx.doi.org/10.1186/s12935-020-01540-0] [PMID: 32943999]
[25]
Ji, B.L.; Xia, L.P.; Zhou, F.X.; Mao, G.Z.; Xu, L.X. Aconitine induces cell apoptosis in human pancreatic cancer via NF-κB signaling pathway. Eur. Rev. Med. Pharmacol. Sci., 2016, 20(23), 4955-4964.
[PMID: 27981537]
[26]
Li, X.M.; Liu, J.; Pan, F.F.; Shi, D.D.; Wen, Z.G.; Yang, P.L. Quercetin and aconitine synergistically induces the human cervical carcinoma HeLa cell apoptosis via endoplasmic reticulum (ER) stress pathway. PLoS One, 2018, 13(1), e0191062.
[http://dx.doi.org/10.1371/journal.pone.0191062] [PMID: 29324796]
[27]
Wang, X.; Lin, Y.; Zheng, Y. Antitumor effects of aconitine in A2780 cells via estrogen receptor β mediated apoptosis, DNA damage and migration. Mol. Med. Rep., 2020, 22(3), 2318-2328.
[http://dx.doi.org/10.3892/mmr.2020.11322] [PMID: 32705198]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy