Effects of Jianpi Huayu Decoction on Th1/Th2 Immune Balance in Mice With Liver Cancer-Related Fatigue via the IL- 27/STAT1 Signaling Pathway

The Chinese medicine Jianpi-Huayu decoction (, JPHY) can alleviate cancer-related fatigue in patients with liver cancer. However, its mechanism remains unclear. In this study, we used BALB/c mice with liver cancer model to investigate whether JPHY alleviates cancer-related fatigue by regulating Th1/...

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Published in:	Integrative cancer therapies Vol. 23; p. 15347354241263018
Main Authors:	Jiayi, Chen, Siru, Chen, Xiaoqi, Luo, Enling, Xu, Hui, Wu, Juze, Lin, Changjun, Wang
Format:	Journal Article
Language:	English
Published:	United States SAGE Publications 01-01-2024 SAGE Publishing
Subjects:	Animals Disease Models, Animal Drugs, Chinese Herbal - pharmacology Fatigue - drug therapy Interleukin-27 Interleukins - metabolism Liver Neoplasms - drug therapy Male Mice Mice, Inbred BALB C Signal Transduction - drug effects STAT1 Transcription Factor - metabolism Th1 Cells - drug effects Th1 Cells - immunology Th1-Th2 Balance - drug effects Th2 Cells - drug effects Th2 Cells - immunology STAT1 phosphorylation IL-27 Jianpi-Huayu decoction cancer-related fatigue inflammatory factors hepatocellular carcinoma
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Summary:	The Chinese medicine Jianpi-Huayu decoction (, JPHY) can alleviate cancer-related fatigue in patients with liver cancer. However, its mechanism remains unclear. In this study, we used BALB/c mice with liver cancer model to investigate whether JPHY alleviates cancer-related fatigue by regulating Th1/Th2 immune balance; and the possible association with the IL-27/STAT1 signaling pathway. We established a mouse model of liver cancer fatigue. Mice were gavaged with physiological saline, low, medium, or high concentrations of JPHY respectively; and intraperitoneal injection of fludarabine (STAT1 pathway inhibitor) with JPHY for 21 days. We recorded the general condition of the mice, and assessed fatigue using scoring criteria and Exhausted Swimming Test. We calculated the spleen and thymus indices, performed H&E staining and immunohistochemical analysis on liver tumor tissues to observe the tumor proliferation marker ki67. We quantified the secretion levels of IFN-γ and IL-2 produced by Th1 cells in serum and splenic lymphocytes, as well as the secretion of IL-4, IL-10 by Th2 cells, and IL-27 in the signaling pathway through ELISA analysis. We evaluated the expression levels of p-STAT1 and STAT1 in spleen tissues using Western blot analysis. JPHY exhibits a therapeutic effect on hepatocellular carcinoma-induced splenomegaly in murine models by upregulating the pro-inflammatory cytokines IFN-γ and IL-2 and downregulating the anti-inflammatory cytokines IL-4 and IL-10. Moreover, JPHY suppresses ki67 expression, reduces tumor-related inflammation infiltration, and ameliorates cancer-associated fatigue. Additionally, the expression of phosphorylated protein p-STAT1 is down-regulated. JPHY may improve the Th1/Th2 immune balance through its anti-inflammatory effects and promotion of IL-27-induced STAT1 phosphorylation, thereby alleviating fatigue in mice with liver cancer.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1534-7354 1552-695X 1552-695X
DOI:	10.1177/15347354241263018