title: Effects of tetrandrine on glioma cell malignant phenotype via inhibition of ADAM17.
abstract: Tetrandrine (TET), a bisbenzylisoquinoline alkaloid isolated from the root of Hang-Fang-Chi (Stephania tetrandra S. Moore), exhibits broad pharmacological effects, including antitumor activity in various malignant neoplasms. Recently, the beneficial effects of TET on cytotoxicity towards tumor cells, radiosensitization, circumventing multidrug resistance, normal tissue radioprotection, and antiangiogenesis have been examined extensively. However, the potential molecular mechanisms of the effect on glioma of TET are yet unknown. This study is explored to evaluate whether TET can inhibit cell proliferation, invasion, and the possible underlying mechanisms in glioma U87 cell. In the present study, cell proliferation was determined by using the Cell Counting Kit-8 (CCK-8) viability assay. The invasion and migration were evaluated by means of wound-scratch assay and Matrigel-Transwell methods. The mRNA expression and protein expression of ADAM metallopeptidase domain 17 (ADAM17) in glioma cell lines and glioma samples were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively. Moreover, the expression of epidermal growth factor receptor (EGFR)/p-EGFR and AKT/p-AKT was studied to clarify the molecular mechanism. Our results suggested that TET inhibited cell proliferation in a dose- and time-dependent manner, and cell migration and invasion in vitro. In addition, our results indicated that ADAM17 expression significantly increased in glioma compared to nontumored human brain tissue and according to the histopathological grade of glioma. Western blot analysis showed that protein expressions of ADAM17, p-EGFR, and p-AKT were inhibited by TET in U87 cells. These data also suggest that suppression of ADAM17 and downregulation of EGFR-phosphoinositide-3-kinase (PI3K)-AKT signaling pathways may contribute to TET-induced decrease of proliferation, migration, and invasiveness.
authors.affiliation: Department of Neurosurgery, The 2nd Affiliated Hospital, Harbin Medical University, Harbin, 150086, China.
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Wu
authors.forename: Guangzhi
authors.initials: G
authors.lastname: Wang
authors.forename: Shaoqian
authors.initials: S
authors.lastname: Xu
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Tian
authors.forename: Hongshuang
authors.initials: H
authors.lastname: Niu
authors.forename: Fei
authors.initials: F
authors.lastname: Yuan
authors.forename: Fenggang
authors.initials: F
authors.lastname: Zhou
authors.forename: Zhen
authors.initials: Z
authors.lastname: Hao
authors.forename: Yongri
authors.initials: Y
authors.lastname: Zheng
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Li
authors.forename: Jianjiao
authors.initials: J
authors.lastname: Wang
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism*; D000072198:ADAM17 Protein; D000970:Antineoplastic Agents / Q000494:pharmacology*; D044182:Benzylisoquinolines / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D044182:Benzylisoquinolines; D012333:RNA, Messenger; C009438:tetrandrine; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human