The upregulation of the anti-apoptotic protein Bcl-2 and downregulation of the pro-apoptotic one Bax, altogether leading to evasion from apoptosis, in association with higher activity of matrix metalloproteinase-9 (MMP-9) and urokinase plasminogen activator (uPA), resulting in higher migration and invasion capacities, were also observed in gemcitabine-resistant CCA cell lines [18]. This evidence concerns the gene PLAU and cholangiocarcinoma.