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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, OBJECTIVE, METHODS, RESULTS. Meshes: Animals, Apoptosis, Bile Duct Neoplasms, Bile Ducts, Intrahepatic, Blotting, Western, Cell Line, Tumor, Cholangiocarcinoma, Estrogen Receptor beta, Gene Expression Regulation, Neoplastic, Humans, In Situ Nick-End Labeling, Liver Neoplasms, Male, Neoplasms, Experimental, RNA, Neoplasm, Rats, Rats, Wistar, Selective Estrogen Receptor Modulators, Treatment Outcome.
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Does an oestrogen receptor β-selective agonist exert anti-neoplastic effects in experimental intrahepatic cholangiocarcinoma? Context: Cholangiocarcinoma cells over-express oestrogen receptor-β, which displays anti-proliferative and pro-apoptotic effects. To evaluate the effects of a newly developed and highly selective oestrogen receptor-β agonist (KB9520) on experimental intrahepatic cholangiocarcinoma. 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. 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.
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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. Final Decision: yes