Abstract
Background
Cholangiocarcinoma cells over-express oestrogen receptor-β, which displays anti-proliferative
and pro-apoptotic effects.
Aim
To evaluate the effects of a newly developed and highly selective oestrogen receptor-β
agonist (KB9520) on experimental intrahepatic cholangiocarcinoma.
Methods
In vitro, the effects of KB9520 on apoptosis and proliferation of HuH-28 cells, HuH-28 cells
with selective oestrogen receptor-β silencing (by small interfering RNA), HepG2 cells
(oestrogen receptor-α and oestrogen receptor-β negative) and HepER3 cells (HepG2 cells
transformed to stably express oestrogen receptor-α) were evaluated.
In vivo, the effects of KB9520 on experimental intrahepatic cholangiocarcinoma, induced by
thioacetamide administration were tested.
Results
In vitro, KB9520 induced apoptosis and inhibited proliferation of HuH-28 cells. KB9520 effects
were absent in cells lacking oestrogen receptor-α and β (HepG2) and in cells expressing
only oestrogen receptor-α (HepER3); its pro-apoptotic effect was impaired in cells
where oestrogen receptor-β expression was decreased by specific small interfering
RNA.
In vivo, KB9520 inhibited experimental intrahepatic cholangiocarcinoma development in thioacetamide-treated
rats and promoted tumour regression in rats where tumour was already established.
In treated animals, tumour areas showed reduced proliferation but increased apoptosis.
Conclusions
KB9520 induced apoptosis in cholangiocarcinoma by selectively acting on oestrogen
receptor-β, suggesting that oestrogen receptor-β selective agonists may be a novel
and effective therapeutic option for the medical treatment of intrahepatic cholangiocarcinoma.
Keywords
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Article Info
Publication History
Published online: July 22, 2011
Accepted:
June 12,
2011
Received:
April 4,
2011
Identification
Copyright
© 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Inc. All rights reserved.
