Mechanisms of Core Chinese Herbs against Colorectal Cancer: A Study Based on Data Mining and Network Pharmacology

Tong Lin,Caijun Liang,Yuqin Qiu,Lisheng Peng,Wenya Peng

doi:10.1155/2020/8325076

Abstract

Colorectal cancer (CRC) is now the second most deadly cancer globally. Chinese herbal medicine (CHM) plays an indispensable role in CRC treatment in China. However, the core herbs (the CHs) in the treatment of CRC and their underlying therapeutic mechanisms remain unclear. This study aims to uncovering the CHs and their mechanisms of action of CRC treatment, applying data mining and network pharmacology approach. First, CHM prescriptions treating CRC were collected from clinical studies from the Chinese National Knowledge Infrastructure (CNKI) and MEDLINE databases, and the CHs were identified through data mining. Then, the bioactive compounds and the corresponding putative targets of the CHs were obtained from three traditional Chinese medicine (TCM) databases. CRC related targets were acquired from three disease databases; the overlapping targets between the CHs and CRC were identified as the therapeutic targets. Subsequently, functional enrichment analysis was performed to elucidate the mechanisms of the CHs on CRC. Moreover, networks were constructed to screen the major bioactive compounds and therapeutic targets. Finally, prognostic values of the major target genes were evaluated by survival analysis, and molecular docking simulation was performed to assess the binding affinity of key targets and major bioactive compounds. It came out that 10 the CHs from 113 prescriptions and 190 bioactive compounds with 118 therapeutic targets were identified. The therapeutic targets were mainly enriched in the biological progress of transcription, apoptosis, and response to cytokine. Various cancer-associated signaling pathways, including microRNAs, TNF, apoptosis, PI3K-Akt, and p53, were involved. Furthermore, 15 major bioactive compounds and five key target genes (VEGFA, CASP3, MYC, CYP1Y1, and NFKB1) with prognostic significance were identified. Additionally, most major bioactive compounds might bind firmly to the key target proteins. This study provided an overview of the anti-CRC mechanisms of the CHs, which might refer to the regulation of apoptosis, transcription, and inflammation.

Highlights

Colorectal cancer (CRC), including colon and rectal cancer, is the third most frequently diagnosed cancer and the second leading cause of cancer-related deaths worldwide [1]
Hereditary accounts for approximately 10–20% of all CRC patients, while 60–65% of CRC cases arise from modifiable risk factors, such as smoking, red and processed meat intake dietary, excessive alcohol intake, and obesity [3]
Clinical Chinese herbal medicine (CHM) prescriptions in the treatment of CRC were collected from studies from the Chinese National Knowledge Infrastructure (CNKI) and MEDLINE databases. e literature search was conducted in topic, title, and abstract, using the following search terms: (“traditional Chinese medicine”) OR (“Chinese herb”∗) OR OR AND AND; the timespan was set from database creation to 1st June 2020

Summary

Introduction

Colorectal cancer (CRC), including colon and rectal cancer, is the third most frequently diagnosed cancer and the second leading cause of cancer-related deaths worldwide [1]. Surgical resection is still the only curative treatment for CRC patients. Due to its occult onset, most CRC patients are diagnosed in advanced stages when surgery is unavailable [4]. Another issue is that major complications occur on up to 15% patients, and postoperative recurrence and metastasis are quite common [4, 5]. Neoadjuvant and adjuvant chemoradiotherapy is generally accepted standard treatment for locally advanced CRC, with the aim of reducing recurrence and metastasis [6,7,8]. Chemoradiotherapy is often confronted with treatment resistance [10]

Methods

Results

Conclusion