Antitumor Effects of a Combined Treatment with Bortezomib and Gemcitabine in Bile Duct Cancer Cell Lines

: Several studies have reported that activation of nuclear factor-kappa B(NF-kB)leads to resistance to chemotherapy and radiotherapy, whereas inhibition of NF-kB activity decreases malignant manifestations and enhances sensitivity to anticancer drugs. In the present study, we used bile duct cancer(BDC)cell lines HuH28 and HuCCT1 to examine if bortezomib, an inhibitor of NF-kB activity, enhances the sensitivity to the currently used chemotherapy drug gemcitabine. We carried out experiments in the following 4 treatment groups: control, 100 nM gemcitabine, 80 nM bortezomib, and a combination of 80 nM bortezomib and 100 nM gemcitabine. Experimental approaches included the MTT assay, apoptosis assay, and western blotting. Forty-eight hours after the treatment, cytotoxic reaction and apoptosis induction were observed in the gemcitabine only and bortezomib only groups. Furthermore, our experiments revealed that the concurrent use of the 2 drugs further increased cytotoxicity and apoptosis. Therefore, because of the NF-kB-inhibiting properties of bortezomib, antitumor immunity could be effectively enhanced. The use of bortezomib increased antitumor effects through multiple signaling pathways. Thus, higher therapeutic efficacy can be achieved through the concurrent use of bortezomib with chemotherapy drugs.