Enhanced efficacy of chemotherapy for XXXX stem cells by simultaneous suppression of multidrug resistance and antiapoptotic cellular defense.

@entity1 @entity632 @entity0 @entity588 @entity5 @entity10430 @entity262 @entity11707 @entity1759 @entity3105 @entity855
UNASSIGNED: While chemotherapy is universally recognized as a frontline treatment strategy for @entity0 , it is not always successful; among the leading causes of treatment failure is existing and/or acquired multidrug resistance. @entity5 stem cells (CSCs), which constitute a minority of the cells of a @entity5 , are acknowledged to be responsible for increased resistance to chemo-drugs through a combination of increased expression of @entity855 -binding cassette transporters (ABC transporters), an increased anti-apoptotic defense, and/or the ability for extensive DNA repair like normal stem cells. Consequently, more effective therapy, especially targeted to CSCs, is urgently required. We studied the characteristics of 231-CSCs ( @entity1759 +/ @entity11707 -) sorted from @entity1 MDA-MB-231 @entity0 cells and demonstrated that 231-CSCs exhibited enhanced capacities for proliferation, migration, tumorigenesis and chemotherapy resistance. To address these multifunctional facets of CSCs, we devised a non-ionic surfactant-based vesicle (niosome) @entity262 to simultaneously deliver siRNAs, targeted to both the ABC transporter ( @entity10430 ) and the anti-apoptosis defense gene ( @entity588 ), and @entity632 ( @entity3105 ) to CSCs. The rationale is to sensitize CSCs to @entity3105 by down regulating the drug-resistance gene @entity10430 and simultaneously induce apoptosis by lowering @entity588 expression. The @entity262 ( @entity262 ) successfully delivered siRNAs and @entity3105 to the cytoplasm and nuclei, respectively, and resulted in a down-regulation of @entity10430 - and @entity588 mRNAs in CSCs by 60% and 65%, respectively, compared to the control. A corresponding decrease in protein expression was observed using Western blotting. The IC50 of @entity3105 in CSCs concurrently decreased significantly. Our result established @entity262 as a promising multi-drug delivery platform for @entity5 treatment.
