Deciphering the Molecular Mechanism of Yifei-Sanjie Pill in Cancer-Related Fatigue

Overview

Journal J Oncol

Specialty Oncology

Date 2023 Feb 23

PMID 36814560

Authors

Yingchao Wu

Shuyao Zhou

Dajin Pi

Yangyang Dong

Wuhong Wang

Huan Ye

Zhongjia Yi

Yiliu Chen

Lizhu Lin

Mingzi Ouyang

Affiliations

Soon will be listed here.

Abstract

Background: The incidence of cancer-related fatigue (CRF) is increasing, but its lack of clear pathogenesis makes its prevention and treatment difficult. Therefore, it is of great significance to clarify the pathogenesis of CRF and find effective methods to treat it.

Methods: The CRF model was established by intraperitoneal injection of LLC cells in ICR mice to explore the pathogenesis of CRF and verify the therapeutic effect of the Yifei-Sanjie pill (YFSJ). The active components of YFSJ were found by LC/MS, the in vitro inflammatory infiltration model of skeletal muscle was constructed by TNF- and C2C12 myoblasts, and the results of in vivo experiments were verified by this model.

Results: Behavioral analysis results showed that YFSJ alleviated CRF; histological examination results showed that YFSJ could reverse the tumor microenvironment leading to skeletal muscle injury; ELISA and RNA-seq results showed that the occurrence of CRF and the therapeutic effect of YFSJ were closely related to the tumor inflammatory microenvironment; IHC and WB results showed that the occurrence of CRF and the therapeutic effect of YFSJ were closely related to the Stat3-related signaling pathway and autophagy.

Conclusions: YFSJ can reduce the level of inflammation in the tumor microenvironment in vivo, inhibit the abnormal activation of the Stat3/HIF-1/BNIP3 signaling pathway induced by tumor-related inflammation, thereby inhibiting the overactivation of mitophagy in skeletal muscle, and finally alleviate CRF. Quercetin, one of the components of YFSJ, plays an important role in inhibiting the phosphorylation activation of Stat3.

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References

Cen X, Wang D, Sun W, Cao L, Zhang Z, Wang B . The trends of mortality and years of life lost of cancers in urban and rural areas in China, 1990-2017. Cancer Med. 2019; 9(4):1562-1571. PMC: 7013076. DOI: 10.1002/cam4.2765. View

Wang Y, Liu N, Lu B . Mechanisms and roles of mitophagy in neurodegenerative diseases. CNS Neurosci Ther. 2019; 25(7):859-875. PMC: 6566062. DOI: 10.1111/cns.13140. View

Cawthon H, Chakraborty R, Roberts J, Backues S . Control of autophagosome size and number by Atg7. Biochem Biophys Res Commun. 2018; 503(2):651-656. DOI: 10.1016/j.bbrc.2018.06.056. View

Wang Z, Wu Z, Xiang Q, Yang J, Xia Z, Hao A . Effects of botanical drugs in the treatment of cancer-related fatigue in patients with gastric cancer: A meta-analysis and prediction of potential pharmacological mechanisms. Front Pharmacol. 2022; 13:979504. PMC: 9490126. DOI: 10.3389/fphar.2022.979504. View

Lan L, Cai Y, Zhang T, Wu R, Xue M, Meng Q . Influencing factors of inpatient expenditure pattern for cancer in China, 2015. Chin J Cancer Res. 2017; 29(1):11-17. PMC: 5348471. DOI: 10.21147/j.issn.1000-9604.2017.01.02. View

Wang X, Feng S, Wang Y, Zhang N, Guo Z, Yan X . Mangiferin, a natural glucoxilxanthone, inhibits mitochondrial dynamin-related protein 1 and relieves aberrant mitophagic proteins in mice model of Parkinson's disease. Phytomedicine. 2022; 104:154281. DOI: 10.1016/j.phymed.2022.154281. View

De Vita F, Orditura M, Auriemma A, Infusino S, Catalano G . Serum concentrations of proinflammatory cytokines in advanced non small cell lung cancer patients. J Exp Clin Cancer Res. 1999; 17(4):413-7. View

Wu Y, Pi D, Chen Y, Zuo Q, Lin L, Ouyang M . Pills Alleviate Chemotherapy-Related Fatigue by Reducing Skeletal Muscle Injury and Inhibiting Tumor Growth in Lung Cancer Mice. Evid Based Complement Alternat Med. 2022; 2022:2357616. PMC: 9423986. DOI: 10.1155/2022/2357616. View

Aartsma-Rus A, van Putten M . Assessing functional performance in the mdx mouse model. J Vis Exp. 2014; (85). PMC: 4158772. DOI: 10.3791/51303. View

10.

Wu Y, Pi D, Chen Y, Zuo Q, Zhou S, Ouyang M . Ginsenoside Rh4 Inhibits Colorectal Cancer Cell Proliferation by Inducing Ferroptosis via Autophagy Activation. Evid Based Complement Alternat Med. 2022; 2022:6177553. PMC: 9168088. DOI: 10.1155/2022/6177553. View

11.

Xu W, Wang S, Sun W, Gao J, Ding X, Kong J . Insufficient radiofrequency ablation-induced autophagy contributes to the rapid progression of residual hepatocellular carcinoma through the HIF-1α/BNIP3 signaling pathway. BMB Rep. 2019; 52(4):277-282. PMC: 6507849. View

12.

Fan P, Xie X, Chen C, Peng X, Zhang P, Yang C . Molecular Regulation Mechanisms and Interactions Between Reactive Oxygen Species and Mitophagy. DNA Cell Biol. 2018; 38(1):10-22. DOI: 10.1089/dna.2018.4348. View

13.

Zhong L, Zhao L, Yang F, Yang W, Sun Y, Hu Q . Evaluation of anti-fatigue property of the extruded product of cereal grains mixed with on mice. J Int Soc Sports Nutr. 2017; 14:15. PMC: 5457539. DOI: 10.1186/s12970-017-0171-1. View

14.

Gkikas I, Palikaras K, Tavernarakis N . The Role of Mitophagy in Innate Immunity. Front Immunol. 2018; 9:1283. PMC: 6008576. DOI: 10.3389/fimmu.2018.01283. View

15.

Yuk J, Silwal P, Jo E . Inflammasome and Mitophagy Connection in Health and Disease. Int J Mol Sci. 2020; 21(13). PMC: 7370205. DOI: 10.3390/ijms21134714. View

16.

Jung J, Kim H, Lee C, Shin Y, Kim Y, Kang G . STAT3 inhibits the degradation of HIF-1alpha by pVHL-mediated ubiquitination. Exp Mol Med. 2008; 40(5):479-85. PMC: 2679355. DOI: 10.3858/emm.2008.40.5.479. View

17.

Filler K, Lyon D, Bennett J, McCain N, Elswick R, Lukkahatai N . Association of Mitochondrial Dysfunction and Fatigue: A Review of the Literature. BBA Clin. 2014; 1:12-23. PMC: 4136529. DOI: 10.1016/j.bbacli.2014.04.001. View

18.

Zhu T, Han J, Yang L, Cai Z, Sun W, Hua Y . Immune Microenvironment in Osteosarcoma: Components, Therapeutic Strategies and Clinical Applications. Front Immunol. 2022; 13:907550. PMC: 9198725. DOI: 10.3389/fimmu.2022.907550. View

19.

Raghav P, Mann Z . Cancer stem cells targets and combined therapies to prevent cancer recurrence. Life Sci. 2021; 277:119465. DOI: 10.1016/j.lfs.2021.119465. View

20.

Wang X, Zhou G, Liu C, Wei R, Zhu S, Xu Y . Acanthopanax 3-Methyladenine Ameliorates Sodium Taurocholate-Induced Severe Acute Pancreatitis by Inhibiting the Autophagic Pathway in Rats. Mediators Inflamm. 2017; 2016:8369704. PMC: 5225378. DOI: 10.1155/2016/8369704. View