Modulation of drug and radiation resistance in XXXX cells by @entity1311 .

@entity137 @entity900 @entity1311 @entity2041 @entity2879 @entity98 @entity151 @entity7737
@entity151 ( @entity151 ) responds to treatment with @entity900 and @entity2879 , but relapse is rapid and survival rates are low. Our aims were to determine the mechanisms of resistance and the potential for @entity1311 ( @entity1311 ) to overcome any drug or radiation resistance. To mimic clinical treatment, H69 @entity151 cells, representative of the classic form of the disease, and H82 cells, with the phenotype of the more resistant variant disease, were treated intermittently with 100 ng/ml @entity900 or 500 ng/ml @entity2879 (approximate IC50 drug doses) to produce stable sublines. Drug and radiation resistance were determined using the @entity98 assay. Protein expression was determined by Western blot. The effect of @entity1311 on drug resistance was determined by @entity137 assays. Intermittent 4-day treatment with 100 ng/ml @entity900 caused 2- to 3-fold resistance to @entity900 (n=5; p<0.05), and 2- to 5-fold cross resistance to @entity2879 , alkylating drugs, the Vinca drugs and radiation. Resistance was mediated primarily by changes in @entity2041 metabolism and was not associated with changes in @entity7737 transport protein. Treatment with @entity2879 (500 ng/ml) produced cells with 2-fold resistance to @entity2879 (n=5; p<0.05). Cross-resistance was limited and mediated by decreased topoisomerase IIalpha. Treatment of both drug-resistant sublines with a maximal non-cytotoxic dose of @entity1311 sensitized them to other drugs and to radiation, although this treatment had no effect on the parental H69 or H82 cells. We conclude that @entity1311 may play an important role in the treatment of refractory @entity151 .
