Article

Establishment of a mouse model of cancer cachexia with spleen deficiency syndrome and the effects of atractylenolide I

Authors: Wan-li Zhang1,2, Na Li3, Qiang Shen1, Men Fan2, Xiao-dong Guo4, Xiong-wen Zhang2, Zhou Zhang3, Xuan Liu1
1 Institute of Interdisciplinary Integrative Biomedical Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
2 Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China
3 Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
4 Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
Correspondence to: Xiong-wen Zhang: xwzhang@sat.ecnu.edu.cn, Zhou Zhang: zzhang@simm.ac.cn, Xuan Liu: xuanliu@shutcm.edu.cn,
DOI: 10.1038/s41401-019-0275-z
Received: 13 February 2019
Accepted: 17 June 2019
Advance online: 24 July 2019

Abstract

Cancer cachexia is a multifactorial metabolic syndrome that affects 50%–80% of cancer patients, and no effective therapy for cancer cachexia is presently available. In traditional Chinese medicine, a large portion of patients with cancer cachexia was diagnosed as spleen deficiency syndrome and treated with tonifying TCMs that produce clinic benefits. In this study we established a new animal model of spleen deficiency and cancer cachexia in mice and evaluated the therapeutic effects of atractylenolide I, an active component of tonifying TCM BaiZhu, in the mouse model. Cancer cachexia was induced in male BALB/c mice by inoculation of mouse C26 colon adenocarcinoma cells, whereas spleen deficiency syndrome was induced by treating the mice with spleen deficiency-inducing factors, including limited feeding, fatigue, and purging. The mouse model was characterized by both cachexia and spleen deficiency characteristics, including significant body weight loss, cancer growth, muscle atrophy, fat lipolysis, spleen, and thymus atrophy as compared with healthy control mice, cancer cachexia mice, and spleen deficiency mice. Oral administration of atractylenolide I (20 mg· kg−1per day, for 30 days) significantly ameliorated the reduction in body weight and atrophy of muscle, fat, spleen, and thymus in mice with spleen deficiency and cachexia. The established model of spleen deficiency and cancer cachexia might be useful in the future for screening possible anticachexia TCMs and clarifying their mechanisms.
Keywords: cancer cachexia; traditional Chinese medicine; spleen deficiency; animal model; muscle atrophy; fat lipolysis; atractylenolide I; metabolic syndrome

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