Administration of suboptimal doses of anticancer drugs not only fails to control @entity5 but often results in increased drug resistance of @entity5 cells. However, little is known about the effects of transient exposure to a minimally cytotoxic dose of chemotherapy on the development of drug resistance of the @entity5 . Previous studies have shown that upregulation of drug-exporter proteins ( @entity855 -binding-cassette proteins) may be one of the key mechanisms involved in inducible drug resistance. In this study, we demonstrated that upregulation of @entity2451 is another possible mechanism. @entity1 cells were exposed to low-dose @entity632 (100 nM; IC(30)) for 3 hr, and then were continuously cultured in drug-free culture media (designated as @entity1 /DR cells). @entity1 /DR cells at up to 9 passages showed increased resistance to @entity632 and cross-resistance to @entity900 . Results of quantitative real-time PCR and flow cytometry assay indicated that the increased drug-resistance in @entity1 /DR cells was not due to upregulation of drug-exporter proteins or to the decrease of intracellular concentration of anticancer drugs. Both the basal and drug-induced @entity2451 activity were shown to be increased in @entity1 /DR cells by EMSA and @entity2451 -driven luciferase reporter gene assay. Suppression of @entity2451 activation by transfection of a dominant negative @entity4284 prevented the development of drug resistance, indicating that the upregulated @entity2451 activity was positively correlated with the low-dose @entity632 -induced drug resistance. These results suggest that even a transient exposure to a small dose of anticancer drugs may induce drug resistance in some @entity5 cells via upregulation of @entity2451 activity.

Involvement of nuclear transcription factor-kappa B in low-dose XXXX -induced drug resistance of cervical carcinoma cells.

@entity1 :: ('9606', 'Species') :: ['SiHa'] @entity632 :: ('MESH:D004317', 'Chemical') :: ['doxorubicin'] @entity2451 :: ('4790', 'Gene') :: ['NF-kappa B'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'tumors', 'cancer'] @entity4284 :: ('4792', 'Gene') :: ['I kappa B alpha'] @entity900 :: ('MESH:D002945', 'Chemical') :: ['cisplatin'] @entity855 :: ('MESH:D000255', 'Chemical') :: ['ATP']
@entity632 :: (MESH:D004317,Chemical) :: ['doxorubicin']
