title: Tetrandrine suppresses human glioma growth by inhibiting cell survival, proliferation and tumour angiogenesis through attenuating STAT3 phosphorylation.
abstract: Tetrandrine (Tet), a bisbenzylisoquinoline alkaloid, has been reported to possess anti-tumour activity. However, its effects on human glioma remain unknown. In this study, we demonstrated that Tet inhibited human glioma cell growth in vitro and in vivo. It has been hypothesised that Tet inhibits glioma growth by affecting glioma cell survival, proliferation and vasculature in and around the xenograft tumour in the chick CAM model and signal transducer and activator of transcription 3 (STAT3) mediated these activities. Therefore, we conducted a detailed analysis of the inhibitory effects of Tet on cell survival using a TUNEL assay and flow cytometric analysis; on cell proliferation based on the expression of proliferating cell nuclear antigen; and on angiogenesis using a CAM anti-angiogenesis assay. We used western blotting to investigate the role of STAT3 on the anti-glioma activities of Tet. The results revealed that Tet inhibited survival and proliferation in human glioma cells, impaired tumour angiogenesis and decreased the expression of phosphorylated STAT3 and its downstream proteins. In sum, our data indicate that STAT3 is involved in Tet-induced the regression of glioma growth by activating tumour cell apoptosis, inhibiting glioma cell proliferation and inhibiting angiogenesis.
authors.affiliation: Division of Pathology, Guangdong Province Key Laboratory of Molecular Immunology and Antibody Engineering, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Ji-Wei
authors.initials: JW
authors.lastname: Ma
authors.affiliation: Division of Pathology, Guangdong Province Key Laboratory of Molecular Immunology and Antibody Engineering, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Division of Pathology, Guangdong Province Key Laboratory of Molecular Immunology and Antibody Engineering, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Ru
authors.initials: R
authors.lastname: Li
authors.affiliation: Division of Pathology, Guangdong Province Key Laboratory of Molecular Immunology and Antibody Engineering, Medical College, Jinan University, Guangzhou 510632, China; Division of Histology & Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Jie-Cheng
authors.initials: JC
authors.lastname: Ye
authors.affiliation: Division of Pathology, Guangdong Province Key Laboratory of Molecular Immunology and Antibody Engineering, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Li
authors.affiliation: Division of Pathology, Guangdong Province Key Laboratory of Molecular Immunology and Antibody Engineering, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Yi-Kai
authors.initials: YK
authors.lastname: Zhang
authors.affiliation: Division of Histology & Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Zheng-Lai
authors.initials: ZL
authors.lastname: Ma
authors.affiliation: Division of Pathology, Guangdong Province Key Laboratory of Molecular Immunology and Antibody Engineering, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Jin-Ying
authors.initials: JY
authors.lastname: Li
authors.affiliation: Division of Pathology, Guangdong Province Key Laboratory of Molecular Immunology and Antibody Engineering, Medical College, Jinan University, Guangzhou 510632, China. Electronic address: tzxy@jnu.edu.cn.
authors.forename: Xue-Yun
authors.initials: XY
authors.lastname: Zhong
authors.affiliation: Division of Histology & Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou 510632, China. Electronic address: yang_xuesong@126.com.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D044182:Benzylisoquinolines / Q000494:pharmacology* / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000187:drug effects / Q000502:physiology; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D044182:Benzylisoquinolines; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C009438:tetrandrine
keywords: Angiogenesis; Apoptosis; CAM; Glioma; Proliferation; STAT3; Tetrandrine