Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 14, 2019; 25(26): 3380-3391
Published online Jul 14, 2019. doi: 10.3748/wjg.v25.i26.3380
Raddeanin A promotes apoptosis and ameliorates 5-fluorouracil resistance in cholangiocarcinoma cells
Shuang-Shuang Guo, Ying Wang, Qing-Xia Fan
Shuang-Shuang Guo, Qing-Xia Fan, Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Shuang-Shuang Guo, Ying Wang, Department of Oncology, First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang 471000, Henan Province, China
Author contributions: Guo SS performed the experiments, analyzed the data, and wrote the manuscript; Wang Y analyzed the data; Fan QX designed the experiments and edited the manuscript.
Institutional review board statement: This study was reviewed and approved by the First Affiliated Hospital of Zhengzhou University.
Conflict-of-interest statement: All authors have nothing to disclose.
Open-Access: 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:
Corresponding author: Qing-Xia Fan, MD, PhD, Doctor, Department of Oncology, the First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Erqi District, Zhengzhou 450052, Henan Province, China.
Telephone: +86-371-66265533 Fax: +86-371-66265533
Received: April 12, 2019
Peer-review started: April 12, 2019
First decision: May 9, 2019
Revised: May 18, 2019
Accepted: May 31, 2019
Article in press: June 1, 2019
Published online: July 14, 2019
Research background

Bile duct cancer is characterized by fast metastasis and invasion and has been thought of as aggressive cancer due to the lack of effective diagnosis at an early stage. The 5-year survival rate of bile duct cancer has not substantially improved in clinical practice. In addition, it is reported that 5-fluorouracil (5-Fu) has been widely applied in treatments for various cancers, achieving a great therapeutic effect. Furthermore, raddeanin A (RA) plays essential proapoptotic roles in various types of tumor cells.

Research motivation

Exploring and developing effective diagnostic ways and therapies for bile duct cancer is greatly urgent for both basic science and clinical management.

Research objectives

The objective of this study was to determine the effects of RA on bile duct cancer cells and the underlying mechanisms.

Research methods

In this study, RA at different concentrations was administered to four cholangiocarcinoma cell lines (RBE, LIPF155C, LIPF178C, and LICCF). Cell viability, Wound-healing migration, Transwell invasion, and Hoechst staining assays were performed to evaluate cell activities. Western blot analysis was performed to the apoptosis-related pathway.

Research results

RA inhibited cell viability in a dose-dependent pattern in the four cell lines. In RBE and LIPF155C cell lines, the migration and colony formation abilities were impaired by RA. Also, RA sensitized cell lines to 5-Fu treatment, promoting the effects of 5-Fu in cholangiocarcinoma cell lines. The role of RA was associated with reduced Wee1 expression. Furthermore, the combinational effect of RA and 5-Fu led to the inhibition of cyclooxygenase-2, B cell lymphoma 2, and Wee1 as well as the elevation of Bax, cyclin D1, and cyclin E.

Research conclusions

RA administration could effectively regulate apoptosis and cell functions in cholangiocarcinoma cell lines in a Wee1-dependent pattern and promote the effect of 5-Fu in bile duct cancer. Collectively, RA is a promising treatment for bile duct cancer.

Research perspectives

This study was aimed to provide clues to the application of RA for the therapy of bile duct cancer.