title: Tetramethylpyrazine inhibits tumor growth of lung cancer through disrupting angiogenesis via BMP/Smad/Id-1 signaling.
abstract: The underlying mechanisms of inhibitory effects induced by tetramethylpyrazine (TMP) on angiogenesis and tumor growth of lung cancer were investigated. In vitro cell proliferation, migration, and tube formation of human microvascular endothelial cells (HMEC-1) were evaluated by a 3-(4,5-dimethylthiazol-2-yl)-2,5-dephenyltetrazolium bromide (MTT), wound healing, Transwell, and Matrigel assays. The expression of BMP/Smad/Id-1 signals was detected by RT-PCR and western blotting. In an A549 xenograft tumor model, TMP (40 and 80 mg/kg/day) was intraperitoneally injected into mice. The expressions of CD31, phosphorylated Smad1/5/8, and Id-1 were measured by immunohistochemistry. We demonstrated that TMP inhibited proliferation, migration, and capillary tube formation of HMEC-1 in a dose- and time-dependent manner. Furthermore, treatment of HMEC-1 cells with TMP (0.4 mg/ml) significantly upregulated BMP2 expression and downregulated BMPRIA, BMPRII, phosphorylated Smad1/5/8, and Id-1 expression. In addition, administrations of TMP remarkably inhibited tumor growth of A549 xenograft in nude mice. The CD31, phosphorylated Smad1/5/8, and Id-1 expression were significantly inhibited in TMP-treated xenograft tumors compared with the vehicle. In conclusion, our results indicated that TMP suppressed angiogenesis and tumor growth of lung cancer via blocking the BMP/Smad/Id-1 signaling.
authors.affiliation: Department of Medical Oncology, General Hospital of Chinese PLA, Beijing 100853, P.R. China.
authors.forename: Youchao
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Medical Oncology, Baoding Hengxing Hospital of Traditional Chinese and Western Medicine, Baoding 071000, P.R. China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Affiliated Hospital of Hebei University, Baoding 071000, P.R. China.
authors.forename: Aimin
authors.initials: A
authors.lastname: Zang
authors.affiliation: Department of Medical Oncology, General Hospital of Chinese PLA, Beijing 100853, P.R. China.
authors.forename: Shunchang
authors.initials: S
authors.lastname: Jiao
authors.affiliation: Department of Medical Oncology, General Hospital of Chinese PLA, Beijing 100853, P.R. China.
authors.forename: Sumei
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, General Hospital of Chinese PLA, Beijing 100853, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Fu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D011719:Pyrazines / Q000008:administration & dosage* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D019485:Bone Morphogenetic Proteins; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D011719:Pyrazines; D051785:Smad Proteins; C017953:tetramethylpyrazine