Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 28, 2019; 25(20): 2463-2472
Published online May 28, 2019. doi: 10.3748/wjg.v25.i20.2463
Brucea javanica oil emulsion improves the effect of radiotherapy on esophageal cancer cells by inhibiting cyclin D1-CDK4/6 axis
Zhong-Hua Qiu, Wei-Wei Zhang, Hong-Hua Zhang, Gui-Hua Jiao
Zhong-Hua Qiu, Wei-Wei Zhang, Gui-Hua Jiao, Department of Interventional Therapy, Affiliated Hospital of Jining Medical University, Jining, 272000, Shandong Province, China
Hong-Hua Zhang, Department of Neurology, Liangshan County People's Hospital, Jining, 272600, Shandong Province, China
Author contributions: Qiu ZH and Jiao GH designed the research; Qiu ZH and Zhang WW performed the research; Zhang HH analyzed the data; Qiu ZH wrote the paper.
Institutional review board statement: This study was reviewed and approved by the Institutional Review Board of Affiliated Hospital of Jining Medical University.
Conflict-of-interest statement: The authors declare no conflict of interest.
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 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/
Corresponding author: Gui-Hua Jiao, MSc, Chief Nurse, Department of Interventional Therapy, Affiliated Hospital of Jining Medical University, Jining 272000, Shandong Province, China. zhqiu123@163.com
Telephone: +86-18853715571 Fax: +86-537-2903918
Received: March 23, 2019
Peer-review started: March 25, 2019
First decision: April 8, 2019
Revised: April 12, 2019
Accepted: May 8, 2019
Article in press: May 8, 2019
Published online: May 28, 2019
Processing time: 66 Days and 23.9 Hours
Abstract
BACKGROUND

Esophageal cancer is one of the most common cancers around the world, and it has high incidence and mortality rates. The conventional therapy for esophageal cancer is radiotherapy, although its effect is highly limited by the resistance of esophageal cancer cells. Thus, strong radiosensitizers can be very crucial during radiotherapy against esophageal cancer. Brucea javanica oil emulsion (BJOE) is a widely used drug against various cancers, such as liver, colon, and ovarian cancer. However, its anti-cancer effect and mechanism and the use of BJOE as a radiosensitizer have not been explored in esophageal cancer.

AIM

To evaluate the anti-cancer effect and mechanism of BJOE and explore the potential use of BJOE as a radiosensitizer during radiotherapy.

METHODS

The inhibitory effect of BJOE and its enhancement function with radiation on cell viability were examined with the calculated half-maximal effective concentration and half-maximal lethal concentration. The influence of BJOE on cell migration and invasion were measured with EC109 and JAR cells by wound-healing and transwell assay. Clonogenesis and apoptotic rate, which was measured by Hoechst staining, were investigated to confirm its enhancement function with radiation. To investigate the molecular pathway underlying the effect of BJOE, the expressions of several apoptosis- and cycle-related proteins was detected by western blotting.

RESULTS

Our results demonstrated that BJOE inhibited the growth of esophageal cancer cell lines more than normal cell lines, and it markedly reduced migration and invasion in esophageal cancer cells (EC109 and JAR). Moreover, it promoted cell apoptosis and enhanced the effect of radiotherapy against esophageal cancerous cells. In the viability test, the values of half-maximal effective concentration and half-maximal lethal concentration were reduced. Compared to the control, only around 1/5 colonies formed when using BJOE and radiation together in the clonogenic assay. The apoptotic rate in EC109 was obviously promoted when BJOE was added during radiotherapy. Our study suggests that the expression of the apoptosis-proteins Bax and p21 were increased, while the expression of Bcl-2 was stable. Further detection of downstream proteins revealed that the expression of cyclin D1 and cyclin-dependent kinase 4/6 were significantly decreased.

CONCLUSION

BJOE has a strong anti-cancer effect on esophageal cancer and can be used as a radiosensitizer to promote apoptosis in cancerous esophageal cells via the cyclin D1-cyclin-dependent kinase 4/6 axis.

Keywords: Esophageal cancer; Brucea javanica oil emulsion; Radiosensitizer; Apoptosis; Cyclin D1-CDK4/6 axis

Core tip:Brucea javanica oil emulsion (BJOE) is a widely used drug against various cancers. However, its anti-cancer effect and potential as a radiosensitizer have not been explored in esophageal cancer. In this study, BJOE reliably inhibited growth, migration, and invasion of esophageal cancerous cells. It was demonstrated that BJOE could be used as a radiosensitizer to promote the apoptosis in esophageal cancerous cells via the cyclin D1-cyclin-dependent kinase 4/6 axis.