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Arctigenin induced gallbladder cancer senescence through modulating epidermal growth factor receptor pathway.
- Source :
-
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine [Tumour Biol] 2017 May; Vol. 39 (5), pp. 1010428317698359. - Publication Year :
- 2017
-
Abstract
- Gallbladder cancer has poor prognosis and limited therapeutic options. Arctigenin, a representative dibenzylbutyrolactone lignan, occurs in a variety of plants. However, the molecular mechanisms involved in the antitumor effect of arctigenin on gallbladder cancer have not been fully elucidated. The expression levels of epidermal growth factor receptor were examined in 100 matched pairs of gallbladder cancer tissues. A positive correlation between high epidermal growth factor receptor expression levels and poor prognosis was observed in gallbladder cancer tissues. Pharmacological inhibition or inhibition via RNA interference of epidermal growth factor receptor induced cellular senescence in gallbladder cancer cells. The antitumor effect of arctigenin on gallbladder cancer cells was primarily achieved by inducing cellular senescence. In gallbladder cancer cells treated with arctigenin, the expression level of epidermal growth factor receptor significantly decreased. The analysis of the activity of the kinases downstream of epidermal growth factor receptor revealed that the RAF-MEK-ERK signaling pathway was significantly inhibited. Furthermore, the cellular senescence induced by arctigenin could be reverted by pcDNA-epidermal growth factor receptor. Arctigenin also potently inhibited the growth of tumor xenografts, which was accompanied by the downregulation of epidermal growth factor receptor and induction of senescence. This study demonstrates arctigenin could induce cellular senescence in gallbladder cancer through the modulation of epidermal growth factor receptor pathway. These data identify epidermal growth factor receptor as a key regulator in arctigenin-induced gallbladder cancer senescence.
- Subjects :
- Adult
Aged
Animals
Apoptosis drug effects
Cell Proliferation drug effects
ErbB Receptors antagonists & inhibitors
Female
Gallbladder Neoplasms genetics
Gallbladder Neoplasms pathology
Gene Expression Regulation, Neoplastic drug effects
Humans
MAP Kinase Signaling System drug effects
Male
Mice
Middle Aged
RNA Interference
Xenograft Model Antitumor Assays
Cellular Senescence drug effects
ErbB Receptors genetics
Furans administration & dosage
Gallbladder Neoplasms drug therapy
Lignans administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1423-0380
- Volume :
- 39
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 28459363
- Full Text :
- https://doi.org/10.1177/1010428317698359