Shikonin Inhibits the Migration and Invasion of Human Glioblastoma Cells by Targeting Phosphorylated β-Catenin and Phosphorylated PI3K/Akt: A Potential Mechanism for the Anti-Glioma Efficacy of a Traditional Chinese Herbal Medicine
Authors: Yi-Xue Xue
Yun-Hui Liu
Zhen-Hua Wang
Feng-Ying Zhang
Ping Wang
Zhong-You Que
Yi Hu
Journal: International journal of molecular sciences (2015)
Discipline: CHEMISTRY
Keywords: glioma; invasion; migration; phosphorylated PI3K/Akt; shikonin
Affiliations: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110122, China. ., Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110122, China. ., Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, China. ., Department of Physiology, College of Basic Medicine, China Medical University, Shenyang 110122, China. .

Abstract:  Shikonin is an anthraquinone derivative extracted from the root of lithospermum. Shikonin is traditionally used in the treatment of inflammatory and infectious diseases such as hepatitis. Shikonin also inhibits proliferation and induces apoptosis in various tumors. However, the effect of shikonin on gliomas has not been fully elucidated. In the present study, we aimed to investigate the effects of shikonin on the migration and invasion of human glioblastoma cells as well as the underlying mechanisms. U87 and U251 human glioblastoma cells were treated with shikonin at 2.5, 5, and 7.5 μmol/L and cell viability, migration and invasiveness were assessed with CCK8, scratch wound healing, in vitro Transwell migration, and invasion assays. The expression and activity of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) and the expression of phosphorylated β-catenin (p-β-catenin) and phosphorylated PI3K/Akt were also checked. Results showed that shikonin significantly inhibited the cell proliferation, migration, invasion, and expression of MMP-2 and MMP-9 in U87 and U251 cells. The expression of p-β-catenin showed contrary trends in two cell lines. It was significantly inhibited in U87 cells and promoted in U251 cells. Results in this work indicated that shikonin displayed an inhibitory effect on the migration and invasion of glioma cells by inhibiting the expression and activity of MMP-2 and -9. In addition, shikonin also inhibited the expression of p-PI3K and p-Akt to attenuate cell migration and invasion and MMP-2 and MMP-9 expression in both cell lines, which could be reversed by the PI3K/Akt pathway agonist, insulin-like growth factor-1 (IGF-1). 

Retracted: No

PubPeer comments:
 Figure 2A and 2B appear to have at least 2 repeated images. I did not check elsewhere in this paper. *** ![file] , 
 Dear Dr. Biskrensis, I am the first author of this paper. I appreciate your interest in our work and your commitment to protecting the accuracy of scientific records. Because I had very limited time to process all my data for submission, I admit there are some oversights in this paper caused by my carelessness. With the request of the corresponding author, I have applied for the retraction of the paper. The retraction process will be arranged by the editors and publishers. I sincerely apologize for the inconvenience it might have caused. More attention would be paid to keep the accuracy of the research papers. Many thanks again for your comment. Sincerely, Fengying Zhang , 
 #2 Could the authors please provide an update on the planned retraction of this paper? I did not see mention of that on the journal website. In addition to the concern raised above, this paper has a number of overlapping or duplicate images used to represent different conditions, similar to the concerns with more than 2 dozen papers with common authorship. Figure 8 shown below as an example. Other papers: https: pubpeer.com search?q=authors%3A%22Yunhui+Liu%22 and https: pubpeer.com search?q=authors%3A%22Yun-hui+Liu%22 (alternate spelling). *** ![file] , 
 #3 Dear Dr. Actinopolyspora Biskrensis, I greatly appreciate your interest in our publications and agree with your comments. For this paper, we had made a response to your comment raised out previously. We had requested a retraction with the journal office three times. However, for then unknown reason, we have not received any response so far. We will sent an email to the journal office to ask for the status of retraction. We will keep you updated. Thank you so much again for your attention to our work. ,