Qi MM, He PZ, Zhang L, Dong WG. STAT3-mediated activation of mitochondrial pathway contributes to antitumor effect of dihydrotanshinone I in esophageal squamous cell carcinoma cells. World J Gastrointest Oncol 2021; 13(8): 893-914 [PMID: 34457194 DOI: 10.4251/wjgo.v13.i8.893]
Corresponding Author of This Article
Wei-Guo Dong, MD, PhD, Professor, Department of Gastroenterology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuhan 430060, Hubei Province, China. dongweiguo@whu.edu.cn
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Oncol. Aug 15, 2021; 13(8): 893-914 Published online Aug 15, 2021. doi: 10.4251/wjgo.v13.i8.893
STAT3-mediated activation of mitochondrial pathway contributes to antitumor effect of dihydrotanshinone I in esophageal squamous cell carcinoma cells
Ming-Ming Qi, Peng-Zhan He, Lan Zhang, Wei-Guo Dong
Ming-Ming Qi, Peng-Zhan He, Lan Zhang, Wei-Guo Dong, Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
Ming-Ming Qi, Peng-Zhan He, Lan Zhang, Central Laboratory of Renmin Hospital, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
Author contributions: Qi MM and Dong WG designed the research; Qi MM and He PZ performed the research; Zhang L contributed new reagents/analytical tools; Qi MM and He PZ analyzed the data; Qi MM wrote the manuscript; all authors have read and approved the final manuscript.
Supported byThe National Natural Science Foundation of China, No. 81572426, No. 81870392, and No. 82000521.
Institutional review board statement: The Ethics Committee of Renmin Hospital of Wuhan University approved all procedures involving animals (WDRM#20181114).
Institutional animal care and use committee statement: All animal experiments were carried out in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Publications No. 8023, revised in 1978).
Conflict-of-interest statement: The authors declare no conflicts of interest for this manuscript.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Wei-Guo Dong, MD, PhD, Professor, Department of Gastroenterology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuhan 430060, Hubei Province, China. dongweiguo@whu.edu.cn
Received: May 20, 2021 Peer-review started: May 20, 2021 First decision: June 12, 2021 Revised: June 17, 2021 Accepted: July 5, 2021 Article in press: July 5, 2021 Published online: August 15, 2021 Processing time: 86 Days and 2.6 Hours
ARTICLE HIGHLIGHTS
Research background
Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies with a poor prognosis. Dihydrotanshinone I (DHTS) has been reported to exert antitumor effect in cancer. However, the role of DHTS in ESCC remains unclear.
Research motivation
This study investigated the role of DHTS in ESCC and the underlying mechanisms, and explored novel therapeutic agents for ESCC.
Research objectives
The aim of this study was to investigate the antitumor effect of DHTS in ESCC and the underlying mechanisms.
Research methods
CCK-8 assay was used to detect proliferation and cell cycle analysis was used to detect cell cycle in ESCC cells. Annexin V-PE/7-AAD double staining assay and Hoechst 33258 staining were used to detect apoptosis. Western blot was used to detect the expression of proteins associated with proliferation and the mitochondrial pathway. Immunofluorescence was used to detect the expression of phosphorylated STAT3 (pSTAT3) in DHTS-treated ESCC cells. ESCC cells with STAT3 knockdown and overexpression were constructed to verify the role of STAT3 in DHTS induced apoptosis. A xenograft tumor model in nude mice was used to evaluate the antitumor effect of DHTS in vivo.
Research results
After treatment with DHTS, the proliferation of ESCC cells was inhibited in a dose- and time-dependent manner. Moreover, DHTS induced cell cycle arrest in the G0/1 phase. Annexin V-PE/7-AAD double staining assay and Hoechst 33258 staining revealed that DHTS induced obvious apoptosis in KYSE30 and Eca109 cells. At the molecular level, DHTS treatment reduced the expression of pSTAT3 and anti-apoptotic proteins, while increasing the expression of pro-apoptotic proteins in ESCC cells. STAT3 knockdown in ESCC cells markedly promoted the activation of the mitochondrial pathway while STAT3 overexpression blocked the activation of the mitochondrial pathway. Additionally, DHTS exerted antitumor effect in a xenograft tumor mouse model.
Research conclusions
DHTS exerts antitumor effect in ESCC via STAT3-mediated activation of the mitochondrial pathway. DHTS may be a novel therapeutic agent for ESCC.
Research perspectives
In the future, additional research will be carried out to further explore the important role of DHTS and whether DHTS treatment can be employed to improve the prognosis of ESCC patients.
