TGF-β signaling is an effective target to impair survival and induce apoptosis of human cholangiocarcinoma cells: A study on human primary cell cultures

TGF-β 信号传导是损害人胆管癌细胞存活和诱导其凋亡的有效靶点:对人原代细胞培养物的研究

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作者:Anna Maria Lustri, Sabina Di Matteo, Alice Fraveto, Daniele Costantini, Alfredo Cantafora, Chiara Napoletano, Maria Consiglia Bragazzi, Felice Giuliante, Agostino M De Rose, Pasquale B Berloco, Gian Luca Grazi, Guido Carpino, Domenico Alvaro

Results

at a dose of 10 μM, CX4945 significantly decreased cell viability of primary human cell cultures from both mucin and mixed CCA, whereas in CK19-positive cell cultures, the effect of CX4945 on cell viability required higher concentrations (>30μM). At the same concentrations, CX4945 also induced apoptosis (3- fold increase vs controls) which correlated with the expression level of CK2 in the different CCA cell lines (mucin- and mixed-CCA). Indeed, no apoptotic effects were observed in CK19-positive cells expressing lower CK2 levels. The effects of CX4945 on viability and apoptosis were associated with an increased number of γ-H2ax (biomarker for DNA double-strand breaks) foci, suggesting the active role of CK2 as a repair mechanism in CCAs. LY2157299 failed to influence cell proliferation or apoptosis but significantly inhibited cell migration. At a 50 μM concentration, in fact, LY2157299 significantly impaired (at 24, 48 and 120 hrs) the wound-healing of primary cell cultures from both mucin-and mixed-CCA. In

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