[Inhibition effect and its mechanism of nobiletin on proliferation of lung cancer cells].
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.
Luo
Gang
G
Department of Pharmacology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China.
Zeng
Yun
Y
Zhu
Ling
L
Zhang
Yi-xian
YX
Zhou
Li-ming
LM
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
D000972:Antineoplastic Agents, Phytogenic; D047309:Flavones; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C008661:nobiletin