Exploring the Mechanism of Action of Canmei Formula Against Colorectal Adenoma Through Multi-Omics Technique

Cui Guo; Xiaoqiang Liu; Yimin Xu; Xinyue Han; Runnan Xie; Xiangxue Meng; Yuan Li; Tongyu Chen; Zhihong Cheng; Xiaoling Fu

doi:10.3389/fcell.2021.778826

Exploring the Mechanism of Action of Canmei Formula Against Colorectal Adenoma Through Multi-Omics Technique

Front Cell Dev Biol. 2021 Nov 29:9:778826. doi: 10.3389/fcell.2021.778826. eCollection 2021.

Authors

Cui Guo^{1

2}, Xiaoqiang Liu^{1

3}, Yimin Xu¹, Xinyue Han¹, Runnan Xie^{1

4}, Xiangxue Meng^{1

2}, Yuan Li¹, Tongyu Chen⁵, Zhihong Cheng⁶, Xiaoling Fu¹

Affiliations

¹ Second Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
² Graduate School of Liaoning University of traditional Chinese Medicine, Shenyang, China.
³ Department of Pain, Shibei Hospital, Shanghai, China.
⁴ Miaohang Town Community Health Service Center, Shanghai, China.
⁵ Cardiothoracic Surgery Department, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
⁶ China State Institute of Pharmaceutical Industry, National Pharmaceutical Engineering Research Center, Shanghai, China.

Abstract

Background: Canmei formula (CMF) is a traditional Chinese medicine compound with definite effect on the prevention and treatment of colorectal adenoma (CRA). CMF can prevent the transformation of intestinal inflammation to cancer. This study explored the mechanism of action of CMF in anti-CRA using multi-omics techniques. Method: The mice were randomly divided into four groups: blank group (Control), high-fat diet (HFD) + AOM/DSS colorectal adenoma model (ADH) groups, Canmei formula treatment group (ADH-CMF) and sulfasalazine treatment group (Sul). Except for the blank group, ADH model was established in the other three groups by intraperitoneal injection with AOM reagent, and then mice were given 2.5% DSS in free drinking water and high-fat diet. The mice in the blank group and ADH groups were intragastrically perfused with normal saline, and the mice in the other two groups were treated with corresponding drugs for 20 weeks. During this period, the changes of physical signs of mice in each group were observed. The differentially expressed genes and proteins in the Control group, ADH group and ADH-CMF group were detected by RNA-seq transcriptome sequencing and Tandem Mass Tags (TMT) quantitative proteomics. After the combined analysis and verification, the key targets were analyzed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Moreover, the changes of intestinal flora in mice of the three groups were examined. Results: A total of 2,548 differential genes were obtained by transcriptomics analysis, and 45 differential proteins were obtained by proteomics analysis. The results of proteomics data and experimental verification showed that CMF mainly affected the Phospholysine Phosphohistidine Inorganic Pyrophosphate Phosphatase (LHPP) target. GO analysis showed that the targets of CMF were involved in the biological processes such as cellular process, metabolic process and biological regulation. KEGG analysis showed that those genes were involved in oxidative phosphorylation, cell senescence, and metabolic pathways. Studies have shown that LHPP overexpression impeded colorectal cancer cell growth and proliferation in vitro, and was associated with a change in PI3K/AKT activity. The results of 16S DNA high-throughput sequencing showed that CMF could effectively regulate the abundance of Bifidobacterium, Candidatus_Saccharimonas and Erysipelatoclostridium in the intestinal flora at the genus level. Conclusion: CMF regulates LHPP via the PI3K/AKT signaling pathway. CMF affects the abundance of specific intestinal flora and can regulate the disorder of intestinal flora to achieve the role of prevention and treatment of CRA.

Keywords: Canmei formula; LHPP; colorectal adenoma; intestinal flora; multi-omics.