CASP8 and cholangiocarcinoma: Consistent with reduced expression of MRP4 and pCHK1, analyses based on immunoblot and cleaved caspase-3 activity assay revealed marked increases in cleaved caspase-3 and caspase-8 expression and caspase activity in CCA cells with SOX9 knockdown, indicating that gemcitabine-induced apoptosis was increased when SOX9 expression was inhibited (Fig. 4g, h).