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Xiaoru Xu,#1 Xiangru Feng,2 Min He,1 Zepeng Zhang,1,3 Jiajia Wang,1 Haiyu Zhu,1 Tie Li,1 Fuchun Wang,1 Mengmeng Sun,corresponding author1,4 and Zhihong Wangcorresponding author1
doi: 10.1186/s13020-020-00315-z
Cancer is a complex systemic disease. As a key component of traditional Chinese medicine, acupuncture is a clinically proven medical treatment for many diseases, and it also has preventative effects as it balances the body, allowing it to self-regulate. For cancer patients, acupuncture is widely used as complementary therapy to boost the immune system and reduce the side effects of radiotherapy and chemotherapy. However, few studies have determined how acupuncture against cancer, especially in regulating the intestinal flora of the tumor-burdened mice.
We treated osteosarcoma tumor-burdened mice by using needling on different acupoints and acupoints combination, thereafter determined the effects of acupuncture on tumor growth by using imaging technology in vitro. In addition, intestinal bacteria were analyzed for further understanding the holistic and systemic treatment effects of acupuncture in osteosarcoma tumor-burdened mice.
Acupuncture treatment can delay tumor growth and changes of intestinal bacteria in osteosarcoma tumor-burdened mice. In detail, the loss of body weight and the development of tumor volume of mice have been postposed by needling specific acupoints. In addition, acupuncture treatment has delayed the changes of the relative abundance of Bacteroidetes, Firmicutes and Candidatus Saccharibacteria at the phylum level. Moreover, the relative abundance of many bacteria (e.g., Catabacter, Acetatifactor and Aestuariispira) has been regulated by using acupuncture treatment, and the trend of structural changes of these bacteria at the genus level has also been postposed compared to that of the tumor-burdened mice model group.
Our results suggest that acupuncture may provide a systemic treatment for cancer. Our findings encourage new and extensive research into the effects of acupuncture on changes of the intestinal microbiome associated with the development of cancer.
Keywords: Acupuncture, Gut microbiota, Xenograft, Osteosarcoma
Cancer is a major public health problem worldwide and is a leading cause of death in both more and less economically developed countries [1]. Accordingly, most recent estimates demonstrate that all countries face huge challenges in managing the very large and increasing burden of cancer, which will only increase in the future [2]. Therefore, the investigation of cancer has become a hot area in scientific research, and various novel biomedical technologies (e.g., genomics, proteomics, and metabolomics) have been used in this area [3–8]. Recently, increasing studies have demonstrated that the gut microbiota plays an important role in regulating of human health and disease by maintaining gut homeostasis [9, 10]. Dysfunction of gut microbiota is associated with many diseases, including gastrointestinal diseases [11–14] and cancer [15, 16]. Microorganisms have important effects on cancer; for example, Helicobacter pylori, hepatitis B and C viruses, and human papillomavirus have been recognized to cause cancer [17–20]. In addition, an increasing number of comparative studies have shown that there are differences in gut microbiota composition between cancer patients and healthy individuals, and the occurrence of cancer often causes or accompanies changes of the intestinal flora [21–23]. Those reported cancers with changes in intestinal flora include not only gastrointestinal cancers (e.g., stomach and colorectal cancer) [15, 16], but other cancer types as well (e.g., pancreas, liver, prostate, and breast cancer) [24–29]. As research provides evidence and expands our understanding of carcinogenic mechanisms, studies on intestinal flora present many more opportunities to develop therapies for cancer diagnosis and management.
Meanwhile, given the widespread cases of cancer worldwide, especially in China [1], an increasing number of complementary and alternative therapies are used in cancer treatment and management. Acupuncture is an important complementary therapy based on the theories and principles of Chinese medicine, it has wide applications and is safe, economical, and convenient with few side effects [30]. To date, acupuncture therapy has been widely used to treat various diseases, such as pain [31], chronic obstructive pulmonary disease [30], breast cancer [32], asthma [33], allergic rhinitis [34], and mild cognitive impairment [35]. The use of acupuncture to treat a variety of conditions associated with disease has attracted the attention of scientists worldwide. In tradition, acupuncture is used to treat diseases caused by blockages of “Qi” and “Xue” [36], which leads to good therapeutic effect of acupuncture on pain [31], including cancer pain [37]. The physiological basis of the analgesic action of acupuncture has been investigated using modern science and technology, and the analgesic effects of acupuncture may attribute to the modulation of the 5-hydroxytryptamine signalling system, the adrenergic system and the N-methyl-d-aspartic acid/AMPA/kainate signalling system etc. [31]. In addition, acupuncture is a comprehensive and holistic treatment. With the development of omics technology, the therapeutic effect of acupuncture has been studied in more diseases (e.g., diseases of digestive system), and some protein and metabolism markers have been found out to indicate the effect of acupuncture by using proteomics and metabolomics [38, 39]. Moreover, many research centers in Europe and the United States have tried to integrate acupuncture with conventional cancer treatment [40, 41]. Currently, the use of acupuncture in cancer has focused on improving the clinical symptoms of cancer patients and reducing the side effects caused by radiotherapy and chemotherapy [42–44]. A few studies have focused on the apoptosis of cancer cells and expression of gene and protein (e.g., CyclinD1 and CDK4) in order to indicate the therapeutic effect of acupuncture on tumor model animals [45–47]. However, research on whether acupuncture can delay the growth and metastasis of tumors in vivo is limited, and the biomedical evidence for acupuncture treatment of cancer also needs to be further explored. Recently, some studies have linked the effects of acupuncture with changes in intestinal flora to study the regulatory effects of acupuncture (or moxibustion) on obesity and ulcerative colitis [48–50]. These studies have suggested that gut microbiota may be a novel target for the effects of acupuncture treatment. Therefore, study of the regulation of intestinal flora combined with treatment effects of acupuncture on cancer in vivo may provide a new view for understanding the therapeutic effect of acupuncture on cancer.
In this research, we treated osteosarcoma tumor-burdened mice by using acupuncture, and determined the effects of acupuncture on tumor growth by using imaging technology in vitro. In addition, the intestinal bacteria were analyzed for further understanding the holistic and systemic treatment effects of acupuncture in osteosarcoma tumor-burdened mice. The results showed acupuncture treatment can delay tumor growth and changes of intestinal bacteria in osteosarcoma tumor-burdened mice, thereby providing new insights into the investigation of acupuncture treatment.
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