Title : Synergistic antitumor activity of gemcitabine and ABT-737 in vitro and in vivo through disrupting the interaction of USP9X and Mcl-1.

Pub. Date : 2011 Jul

PMID : 21566062






5 Functional Relationships(s)
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1 The Bcl-2 antagonist ABT-737 targets Bcl-2/Bcl-xL, but not Mcl-1, which may confer resistance to this agent in various cancers with high levels of Mcl-1. 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid MCL1 apoptosis regulator, BCL2 family member Homo sapiens
2 Importantly, in ABT-737-resistant cancer cells, the interaction between USP9X and Mcl-1, which was increased by ABT-737 treatment, could be disrupted by gemcitabine, thus resulting in enhanced ubiquitination and the subsequent degradation of Mcl-1 and ultimately in the synergism of these two drugs. 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid MCL1 apoptosis regulator, BCL2 family member Homo sapiens
3 Importantly, in ABT-737-resistant cancer cells, the interaction between USP9X and Mcl-1, which was increased by ABT-737 treatment, could be disrupted by gemcitabine, thus resulting in enhanced ubiquitination and the subsequent degradation of Mcl-1 and ultimately in the synergism of these two drugs. 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid MCL1 apoptosis regulator, BCL2 family member Homo sapiens
4 Importantly, in ABT-737-resistant cancer cells, the interaction between USP9X and Mcl-1, which was increased by ABT-737 treatment, could be disrupted by gemcitabine, thus resulting in enhanced ubiquitination and the subsequent degradation of Mcl-1 and ultimately in the synergism of these two drugs. 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid MCL1 apoptosis regulator, BCL2 family member Homo sapiens
5 Importantly, in ABT-737-resistant cancer cells, the interaction between USP9X and Mcl-1, which was increased by ABT-737 treatment, could be disrupted by gemcitabine, thus resulting in enhanced ubiquitination and the subsequent degradation of Mcl-1 and ultimately in the synergism of these two drugs. 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid MCL1 apoptosis regulator, BCL2 family member Homo sapiens