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

Bile duct cancer is characterized by fast metastasis and invasion and has been regarded as one of the most aggressive tumors due to the absence of effective diagnosis at an early stage. Therefore, it is in the urgent demand to explore novel diagnostic approaches and therapeutic strategies for bile duct cancer to improve patient survival. Raddeanin A (RA) is extracted from the anemone raddeana regel and has been demonstrated to play antitumor roles in various cancers.


To investigate the effects of RA treatment on bile duct cancer cells.


In this study, four cholangiocarcinoma cell lines (RBE, LIPF155C, LIPF178C, and LICCF) treated with RA were used to test the cell viability. The RA-associated cell functional analysis, 5-fluorouracil (5-Fu) effectiveness as well as cell cycle- and apoptosis-related protein expression were investigated.


RA reduced cell viability in a dose-dependent pattern in four cell lines, and the migration and colony formation abilities were also impaired by RA in RBE and LIPF155C cell lines. RA sensitized cell lines to 5-Fu treatment and enhanced the effects of 5-Fu in cholangiocarcinoma. Also, RA decreased protein expression of Wee1, while the combinational effect of RA and 5-Fu decreased protein expressions of cyclooxygenase-2, B cell lymphoma 2, and Wee1 but increased protein levels of Bax, cyclin D1, and cyclin E.


Taken together, the results suggest that RA acts as an anti-cancer agent and enhancer of 5-Fu in bile duct cancer cells via regulating multiple cell cycle and apoptosis-related proteins. This finding provides novel clues to exploring a novel antitumor drug for bile duct cancer.

Keywords: Bile duct cancer, Raddeanin A, 5-fluorouracil, Cell cycle, Apoptosis

Core tip: We report that raddeanin A (RA) reduced cell viability, migration, and colony formation abilities in cholangiocarcinoma cells and enhanced the antitumor effect of 5-Fu in cholangiocarcinoma cells. This study also demonstrated that the anticancer effects of RA were associated with apoptosis-related proteins Bax and B cell lymphoma 2 as well as cell cycle-related proteins Wee1, cyclin D1, cyclin E, and cyclooxygenase-2.