title: Glycyrrhizin suppresses lung adenocarcinoma cell growth through inhibition of thromboxane synthase.
abstract: OBJECTIVE
  The effects of glycyrrhizin treatment in lung cancer remain undetermined, despite extensive studies of the anti-tumor activities of glycyrrhizin.
  
  
  METHODS
  Lung adenocarcinoma A549 and NCI-H23 cell lines were used in this study. Cell growth was examined by MTS assays, while apoptosis and cell cycle were determined by flow cytometric analysis. Both real-time PCR and western blotting were used to examine the expression levels of thromboxane synthase (TxAS), and TxAS activity was measured using EIA detection of the biosynthesis of TxA2. TxAS was overexpressed in NCI-H23 cells by transfection with TxAS cDNA, while TxAS was inhibited by transfection with TxAS siRNA in A549 cells. For the mouse model of lung adenocarcinoma, the effects of glycyrrhizin on tumor growth were analyzed by western blot evaluation of TxAS, PTEN and survivin. TxAS activity was determined by EIA assay.
  
  
  RESULTS
  Glycyrrhizin suppressed cell growth in A549 cells, but not in NCI-H23 cells, by induction of apoptosis. TxAS was overexpressed in A549 cells, but the TxAS levels in NCI-H23 cells were minimal. Moreover, TxAS expression and activity were suppressed by glycyrrhizin. Glycyrrhizin had no additive effects with TxAS siRNA knockdown in suppressing A549 cell growth, whereas it completely suppressed cell growth of NCI-H23 cells transfected with TxAS cDNA. These results were further confirmed by the in vivo study.
  
  
  CONCLUSIONS
  Our study suggests that the anti-tumor effect of glycyrrhizin in lung adenocarcinoma is, at least in part, TxAS-dependent. Therefore, glycyrrhizin is a promising anti-cancer agent for the treatment of lung adenocarcinoma.
authors.affiliation: Department of Rheumatology, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China.
authors.forename: Run-Yue
authors.initials: RY
authors.lastname: Huang
authors.forename: Yong-Liang
authors.initials: YL
authors.lastname: Chu
authors.forename: Ze-Bo
authors.initials: ZB
authors.lastname: Jiang
authors.forename: Xiu-Ming
authors.initials: XM
authors.lastname: Chen
authors.forename: Xian
authors.initials: X
authors.lastname: Zhang
authors.forename: Xing
authors.initials: X
authors.lastname: Zeng
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D013930:Thromboxane-A Synthase / Q000235:genetics / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D019695:Glycyrrhizic Acid; D013930:Thromboxane-A Synthase