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• W2912742022 endingPage "e0210077" @default.
• W2912742022 startingPage "e0210077" @default.
• W2912742022 abstract "Cholangiocarcinoma (CCA) is an aggressive cancer with high resistance to chemotherapeutics. CCA is enriched in cancer stem cells, which correlate with aggressiveness and prognosis. FXR, a member of the metabolic nuclear receptor family, is markedly down-regulated in human CCA. Our aim was to evaluate, in primary cultures of human intrahepatic CCA (iCCA), the effects of the FXR agonist obeticholic acid (OCA), a semisynthetic bile acid derivative, on their cancerogenic potential. Primary human iCCA cell cultures were prepared from surgical specimens of mucinous or mixed iCCA subtypes. Increasing concentrations (0–2.5 μM) of OCA were added to culture media and, after 3–10 days, effects on proliferation (MTS assay, cell population doubling time), apoptosis (annexin V-FITC/propidium iodide), cell migration and invasion (wound healing response and Matrigel invasion assay), and cancerogenic potential (spheroid formation, clonogenic assay, colony formation capacity) were evaluated. Results: FXR gene expression was downregulated (RT-qPCR) in iCCA cells vs normal human biliary tree stem cells (p < 0.05) and in mucinous iCCA vs mixed iCCA cells (p < 0.05) but was upregulated by addition of OCA. OCA significantly (p < 0.05) inhibited proliferation of both mucinous and mixed iCCA cells, starting at a concentration as low as 0.05 μM. Also, CDCA (but not UDCA) inhibited cell proliferation, although to a much lower extent than OCA, consistent with its different affinity for FXR. OCA significantly induced apoptosis of both iCCA subtypes and decreased their in vitro cancerogenic potential, as evaluated by impairment of colony and spheroid formation capacity and delayed wound healing and Matrigel invasion. In general, these effects were more evident in mixed than mucinous iCCA cells. When tested together with Gemcitabine and Cisplatin, OCA potentiated the anti-proliferative and pro-apoptotic effects of these chemotherapeutics, but mainly in mixed iCCA cells. OCA abolished the capacity of both mucinous and mixed iCCA cells to form colonies when administered together with Gemcitabine and Cisplatin. In subcutaneous xenografts of mixed iCCA cells, OCA alone or combined with Gemcitabine or Cisplatin markedly reduced the tumor size after 5 weeks of treatment by inducing necrosis of tumor mass and inhibiting cell proliferation. In conclusion, FXR is down-regulated in iCCA cells, and its activation by OCA results in anti-cancerogenic effects against mucinous and mixed iCCA cells, both in vitro and in vivo. The effects of OCA predominated in mixed iCCA cells, consistent with the lower aggressiveness and the higher FXR expression in this CCA subtype. These results, showing the FXR-mediated capacity of OCA to inhibit cholangiocarcinogenesis, represent the basis for testing OCA in clinical trials of CCA patients." @default.
• W2912742022 created "2019-02-21" @default.
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• W2912742022 date "2019-01-24" @default.
• W2912742022 modified "2023-10-18" @default.
• W2912742022 title "The FXR agonist obeticholic acid inhibits the cancerogenic potential of human cholangiocarcinoma" @default.
• W2912742022 cites W1889915419 @default.
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• W2912742022 cites W1981608445 @default.
• W2912742022 cites W1982449570 @default.
• W2912742022 cites W1992149176 @default.
• W2912742022 cites W2007086626 @default.
• W2912742022 cites W2021998283 @default.
• W2912742022 cites W2022279737 @default.
• W2912742022 cites W2023678020 @default.
• W2912742022 cites W2024058225 @default.
• W2912742022 cites W2025988357 @default.
• W2912742022 cites W2028700227 @default.
• W2912742022 cites W2029854125 @default.
• W2912742022 cites W2032561291 @default.
• W2912742022 cites W2040709804 @default.
• W2912742022 cites W2047711197 @default.
• W2912742022 cites W2049515100 @default.
• W2912742022 cites W2053581007 @default.
• W2912742022 cites W2059634098 @default.
• W2912742022 cites W2061942275 @default.
• W2912742022 cites W2073996314 @default.
• W2912742022 cites W2089133296 @default.
• W2912742022 cites W2102459969 @default.
• W2912742022 cites W2108730917 @default.
• W2912742022 cites W2115261608 @default.
• W2912742022 cites W2119028086 @default.
• W2912742022 cites W2124532015 @default.
• W2912742022 cites W2132302780 @default.
• W2912742022 cites W2132593028 @default.
• W2912742022 cites W2141078344 @default.
• W2912742022 cites W2146625285 @default.
• W2912742022 cites W2158609797 @default.
• W2912742022 cites W2158611031 @default.
• W2912742022 cites W2159415303 @default.
• W2912742022 cites W2159496628 @default.
• W2912742022 cites W2164858484 @default.
• W2912742022 cites W2171398834 @default.
• W2912742022 cites W2177450918 @default.
• W2912742022 cites W2318933482 @default.
• W2912742022 cites W2337387091 @default.
• W2912742022 cites W2342609081 @default.
• W2912742022 cites W2485417128 @default.
• W2912742022 cites W2535490199 @default.
• W2912742022 cites W2603375353 @default.
• W2912742022 cites W2606348958 @default.
• W2912742022 cites W2606475547 @default.
• W2912742022 cites W2736009495 @default.
• W2912742022 cites W2746886892 @default.
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• W2912742022 cites W2765410098 @default.
• W2912742022 cites W2804699234 @default.
• W2912742022 cites W2977732097 @default.
• W2912742022 cites W4243304942 @default.
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• W2912742022 doi "https://doi.org/10.1371/journal.pone.0210077" @default.
• W2912742022 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6345424" @default.
• W2912742022 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30677052" @default.
• W2912742022 hasPublicationYear "2019" @default.
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