Role of aldo-keto reductases and other doxorubicin pharmacokinetic genes in doxorubicin resistance, DNA binding, and subcellular localization.

Since the AKR inhibitor 5β-cholanic acid is a well-tolerated naturally occurring bile acid in humans, and since flufenamic acid has been used in clinical trials with manageable toxicities [ 41 ], there may be significant value in conducting clinical trials in which either 5β-cholanic acid or flufenamic acid are co-administered with doxorubicin during chemotherapy.

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These differences relative to untreated cells were found to be highly significant, and are likely due to the increased expression of AKRs [ 17 ] and ABC drug transporters known to be over-expressed in MCF-7 DOX2-12 cells, including Abcc1 [ 27 ].

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