Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jul 15, 2024; 16(7): 3193-3210
Published online Jul 15, 2024. doi: 10.4251/wjgo.v16.i7.3193
Baitouweng decoction suppresses growth of esophageal carcinoma cells through miR-495-3p/BUB1/STAT3 axis
Hui Yang, Xiao-Wei Chen, Xue-Jie Song, Hai-Yang Du, Fu-Chun Si
Hui Yang, Xiao-Wei Chen, Xue-Jie Song, Hai-Yang Du, Fu-Chun Si, Henan Key Laboratory of Traditional Chinese Medicine Syndrome and Prescription in Signaling, Henan International Joint Laboratory of TCM Syndrome and Prescription in Signaling, Traditional Chinese Medicine School, Henan University of Chinese Medicine, Zhengzhou 450046, Henan Province, China
Author contributions: Yang H wrote the manuscript and analyzed the data; Si FC participated in the study design and interpretation; Chen XW and Yang H performed the experiments; Song XJ and Du HY acquired and analyzed the data; all the authors have read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 81550014; Henan Provincial Science and Technology Research Project, No. 222102310187 and No. 242102310582; and Henan Province Postdoctoral Research Project, No. 202103092.
Institutional review board statement: The study was reviewed and approved by The First Affiliated Hospital of Henan University of Chinese Medicine.
Conflict-of-interest statement: The authors declare that they have no competing interests to disclose.
Data sharing statement: Technical appendix, statistical code, and dataset are available from the corresponding author at sifc2000@hotmail.com.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Fu-Chun Si, PhD, Professor, Henan Key Laboratory of Traditional Chinese Medicine Syndrome and Prescription in Signaling, Henan International Joint Laboratory of TCM Syndrome and Prescription in Signaling, Traditional Chinese Medicine School, Henan University of Chinese Medicine, No. 156 Jinshui East Road, Zhengdong New District, Zhengzhou 450046, Henan Province, China. sifc2000@hotmail.com
Received: January 20, 2024
Revised: April 29, 2024
Accepted: June 4, 2024
Published online: July 15, 2024
Processing time: 174 Days and 8.5 Hours
Abstract
BACKGROUND

Esophageal carcinoma (EC) is one of the most prevalent cancers in human populations worldwide. Baitouweng decoction is one of the most important Chinese medicine formulas, with the potential to treat cancer.

AIM

To investigate the role and mechanism of Baitouweng decoction on EC cells.

METHODS

Differentially expressed genes (DEGs) in EC tissues and normal tissues were screened by the cDNA microarray technique and by bioinformatics methods. The target genes of microRNAs were predicted based on the TargetScan database and verified by dual luciferase gene reporter assay. We used Baitouweng decoction to intervene EC cells, and detected the activity of EC9706 and KYSE150 cells by the MTT method. Cell cycle and apoptosis were measured by flow cytometry. The expression of BUB1 mRNA and miR-495-3p was measured by qRT-PCR. The protein levels of BUB1, STAT3, p-STAT3, CCNB1, CDK1, Bax, Caspase3, and Caspase9 were measured by Western blot analysis. The migration and invasion abilities of the cells were measured by wound-healing assay and Transwell invasion assay, respectively.

RESULTS

DEGs identified are involved in biological processes, signaling pathways, and network construction, which are mainly related to mitosis. BUB1 was the key hub gene, and it is also a target gene of miR-495-3p. Baitouweng decoction could upregulate miR-495-3p and inhibit BUB1 expression. In vitro experiments showed that Baitouweng decoction significantly inhibited the migration and invasion of EC cells and induced apoptosis and G2/M phase arrest. After treatment with Baitouweng decoction, the expression of Bax, Caspase 3, and Caspase 9 in EC cells increased significantly, while the expression of BUB1, CCNB1, and CDK1 decreased significantly. Moreover, the STAT3 signaling pathway may play an important role in this process.

CONCLUSION

Baitouweng decoction has a significant inhibitory effect on EC cell growth. BUB1 is a potential therapeutic target for EC. Further analysis showed that Baitouweng decoction may inhibit the growth of EC cells by upregulating miR-495-3p targeting the BUB1-mediated STAT3 signal pathway.

Keywords: Baitouweng decoction; Esophageal cancer; miR-495-3p; BUB1; STAT3 signaling pathway

Core Tip: Differentially expressed genes in esophageal carcinoma (EC) were analyzed and BUB1 was found to be a key hub gene. BUB1 is a target gene of miR-495-3p, and BUB1 can directly interact with STAT3 to inhibit tumor cell proliferation. We studied the effects of Baitouweng decoction on the cell cycle, apoptosis, migration, and invasion, and further investigated the inhibitory effect of Baitouweng decoction on the development of EC by targeting BUB1 and STAT3 via miR-495-3p. The potential functional pathways were explored.