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[Studies on the mechanism of multidrug resistance].

Authors
Type
Published Article
Journal
Gan to kagaku ryoho. Cancer & chemotherapy
Publication Date
Volume
14
Issue
3 Pt 2
Pages
807–814
Identifiers
PMID: 3471182
Source
Medline

Abstract

We have introduced two different approaches which we have introduced recently in an attempt to understand the mechanism of multidrug resistance, which was shown to be successfully reversed using non-antitumor analogs of anthracycline and vinca alkaloid. This approach was adopted on the basis of our hypothesis that these substances can inhibit the accelerated drug efflux of the resistant cells. On the other hand, we found that such efflux consists of a saturable as well as an unsaturable process using our newly-designed kinetic approach. In addition, greater Vmax and lower Km were found in the saturable process of efflux in resistant cells as compared with those in sensitive cells. In conclusion, these results suggest that broad cross-resistance among structurally unrelated drugs, i.e., multidrug resistance, is associated with an efflux-oriented transport carrier with broad affinity for these lipophilic drugs with a polycyclic structure.

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