title: Inhibition of cyclooxygenase-2 by tetramethylpyrazine and its effects             on A549 cell invasion and metastasis.
abstract: Cyclooxygenase (COX)-2 plays an important role in tumorigenesis and has been implicated to be a critical factor for invasion and metastasis of lung cancer. Tetramethylpyrazine (TMP), an effective component of the traditional Chinese medicine Chuanxiong, has been traditionally used in treating neurovascular and cardiovascular diseases. Recently TMP has been reported to have beneficial effect in cancer patients. However, the function and the mechanism of TMP in lung cancer have not been elucidated to date. In this study, we investigated the in vitro and in vivo effect of TMP in tumorigenesis and whether COX-2 is a molecular target of TMP. We showed that TMP exhibited a dose- and time-dependent inhibition on A549 cell proliferation by suppressing cell cycle progression. In vitro treatment of A549 cells with TMP resulted in a significant inhibition of invasion, associated with reduced activities of COX-2 and MMP-2/TIMP-2. Furthermore, in vivo experiments showed that TMP significantly suppressed metastatic growth of A549 cells and COX-2 expression in metastatic nude mouse model. This preclinical study provides the first evidence for the novel anti-tumor effects of TMP as a COX-2 pathway inhibitor in human adenocarcinoma cell line A549. These studies suggest that TMP may serve as an effective agent for the treatment and chemoprevention of non-small cell lung cancer.
authors.affiliation: Department of Respiratory Medicine, Qilu Hospital, Shandong University,                     Jinan 250012, P.R. China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Zheng
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
authors.forename: Mao-Xiang
authors.initials: MX
authors.lastname: Zhu
authors.forename: Xiu-Jie
authors.initials: XJ
authors.lastname: Pan
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Yang
authors.forename: Sheng-Yu
authors.initials: SY
authors.lastname: Zhou
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000556:secondary; D000818:Animals; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008558:Melphalan / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D011719:Pyrazines / Q000494:pharmacology* / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D007074:Immunoglobulin G; D011719:Pyrazines; C051713:antineoplastic agent K 18; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D015232:Dinoprostone; D008558:Melphalan; C017953:tetramethylpyrazine