title: [Inhibition effect and its mechanism of nobiletin on proliferation of lung cancer cells].
abstract: OBJECTIVE
  To investigate inhibition effect and its mechanism of Nobiletin on the proliferation of lung cancer cells in vivo and in vitro.
  
  
  METHODS
  Human lung adenocarcinoma cell line A549 was treated with various dose of Nobiletin, and cell proliferation was tested by MTT assay. DNA damage of A549 cells was detected by comet assay. Expression of Bcl-2 and Bax proteins were analyzed by Western blot assay. Lewis lung carcinoma (LLC) models were established in C57BL/6 mice and treated with Nobiletin once a day for 12 d, and then the inhibitory rate of tumor growth was measured. Cellular apoptosis was determined using TUNEL assay. The protein levels of Bax, Bcl-2 and Caspase-9 in LLC tissues were determined by immunohistochemistry.
  
  
  RESULTS
  The treatment of Nobiletin resulted in significant inhibition of A549 cells proliferation in a dose-dependent manner. Comet assay revealed that DNA damage increased along with the increase of Nobiletin dosage. Western blot analysis showed that A549 cells pretreated with Nobiletin had Bcl-2 protein expression decreased and Bax protein expression increased. The inhibitory rates of lung carcinoma were 43.70%, 27.59% and 20.14% in lewis mice treated with high (300 mg/kg), middle (200 mg/kg), and low (100 mg/kg) dosage of Nobiletin (P<0.01). With the treatment of Nobiletin, the expression of Bax and Caspase-9 proteins increased, and the expression of Bcl-2 proteins decreased.
  
  
  CONCLUSIONS
  Nobiletin has certain inhibitory effects on the proliferation of lung cancer cells both in vivo and in vitro. The mechanism may be related to up-regulation of Bax and Caspase-9 and down-regulation of Bcl-2.
authors.affiliation: Department of Pharmacology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Luo
authors.forename: Yun
authors.initials: Y
authors.lastname: Zeng
authors.forename: Ling
authors.initials: L
authors.lastname: Zhu
authors.forename: Yi-xian
authors.initials: YX
authors.lastname: Zhang
authors.forename: Li-ming
authors.initials: LM
authors.lastname: Zhou
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D018827:Carcinoma, Lewis Lung / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D047309:Flavones / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D047309:Flavones; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C008661:nobiletin