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A previously established arsenite-resistant cell line, KAS, is also resistant to a variety of anticancer drugs. In order to understand responsible molecules for the multidrug resistance phenotype of KAS cells, we examined the expressions of ATP-binding cassette (ABC) transporters and found that the ABCB6 and ABCC1/ multidrug resistance protein 1 (ABCC1/MRP1) were increased. ABCC1/MRP1 was not completely responsible for the drug resistance spectrum of KAS cells and several reports have suggested that ABCB6 is related to anticancer drug and metal resistance. We, therefore, established and examined ABCB6-expressing KB cells and ABCB6-knockdown KAS cells. ABCB6 expression enhanced resistance to 5-fluorouracil (5-FU), SN-38 and vincristine (Vcr) but not to arsenite. Conversely, down-regulation of ABCB6 in KAS cells increased the sensitivity of KAS cells to 5-FU, SN-38 and Vcr, but not to arsenite. Our findings suggest that ABCB6 is involved in 5-FU, SN-38 and Vcr resistance.

Gefitinib and erlotinib are inhibitors of epidermal growth factor receptor tyrosine kinase. The effects of these tyrosine kinase inhibitors on RAS-mutated cancer cells are unclear.Influence of gefitinib and erlotinib treatment was examined in H23 adenocarcinoma and A431 epidermoid carcinoma cells. The WST-1 assay was performed for evaluating cell growth. The phosphorylation status of extracellular-signal-regulated kinases (ERK) and AKT (protein kinase B) was examined by western blot. Flow cytometry was used for analyzing cell-cycle status and apoptosis detection.In H23 cells, 20 μM erlotinib suppressed growth, while gefitinib did not suppress proliferation after 48 h of treatment. Neither gefitinib nor erlotinib affected the phosphorylation of ERK and AKT in H23 cells. Erlotinib augmented the sub-G1 population of H23 cells, while gefitinib reduced it.In H23 cells, erlotinib accelerated apoptosis, while gefitinib induced G1 arrest.