title: RETRACTED: 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.
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).
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110122, China. zhangfengyingcmu@163.com.|Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110122, China. zhangfengyingcmu@163.com.
authors.forename: Feng-Ying
authors.initials: FY
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, China. hooyie@hotmail.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, China. 18840042401@163.com.
authors.forename: Zhong-You
authors.initials: ZY
authors.lastname: Que
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110122, China. pingwang8000@163.com.|Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110122, China. pingwang8000@163.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, China. liuyunhuicmu@aliyun.com.
authors.forename: Yun-Hui
authors.initials: YH
authors.lastname: Liu
authors.affiliation: Department of Physiology, College of Basic Medicine, China Medical University, Shenyang 110122, China. hooyie@sohu.com.
authors.forename: Zhen-Hua
authors.initials: ZH
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110122, China. yxxue@mail.cmu.edu.cn.|Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110122, China. yxxue@mail.cmu.edu.cn.
authors.forename: Yi-Xue
authors.initials: YX
authors.lastname: Xue
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D007334:Insulin-Like Growth Factor I; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000378:metabolism; D008516:Medicine, Chinese Traditional; D009285:Naphthoquinones / Q000494:pharmacology*; D009361:Neoplasm Invasiveness / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D051176:beta Catenin / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D007334:Insulin-Like Growth Factor I; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D009285:Naphthoquinones; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D051176:beta Catenin; C583557:IGF1 protein, human; C016101:shikonin; C522361:MMP2 protein, human; C579270:MMP9 protein, human
keywords: glioma; invasion; migration; phosphorylated PI3K/Akt; shikonin; β-catenin