Characterization of the Effect of Several Drugs Which May Be Useful in Chemotherapy Treatments on the Level of MDRI mRNA Expression
Stackpole, Jonathan J.
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The phenomenon of multidrug resistance in cancer cells often causes the failure of chemotherapy. In this study, compounds which have been suspected to have the capability of modulating the multidrug resistance (MDR) phenotype at the mRNA level were tested on Chinese Hamster Ovary (CHRC5) cells and human cancer (KB-Vl) cells. It was found that the cyclic AMP-dependent protein kinase (PK-A) inhibitors, K252a, H -7, and staurosporine, inhibited the production of MDR 1 mRNA in CHRC5 cells. The PK-A inhibitors, H-7 and staurosporine, also caused a significant decrease in MDR 1 mRNA production in the KB-Vl cell line. The adenylate cyclase activator, forskolin caused an increased level of MDR 1 mRN A. The cAMP analogue, 8-Br-cAMP, caused a decrease in MDRI mRNA levels in the CHRC5 cell line. 4-𝛽 myristate 13-α. acetate (PMA) showed an increased MDR1 level in the CHRC5 cell line, however it showed a decreased MDR1 level in the KB-Vl cells. Treatment of the CHR C5 cell line with the phosphatase inhibitor okadaic acid resulted in increased levels of MDRI mRNA. Two cyclopropylpyrroloindole (CPI) derivatives, CC-I065 and U- 80244, showed an increased MDRI level in the CHRC5 cell line. No significant change was seen in the KB-VI cell line. The calmodulin inhibitor, W -7, caused an variable response pattern of the MDRI mRNA level in the CHRC5 cell line.