Journal
ONCOLOGY REPORTS
Volume 32, Issue 4, Pages 1647-1653Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2014.3365
Keywords
genistein; MCF-7/Adr; reversal of multidrug resistance; doxorubicin
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Funding
- Science Career Development Foundation of Hubei Medical College [2007ZQB14]
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The molecular mechanisms underlying genistein-mediated reversal of chemoresistance remains unknown. In the present study, we investigated the molecular mechanisms by which genistein overcomes chemoresistance and its effect on doxorubicin-induced cytotoxicity. Consistent with previous reports, genistein combined with doxorubicin had a synergistic effect on MCF-7/Adr cells, and genistein reduced the chemoresistance of these cells. Genistein treatment increased the intracellular accumulation of doxorubicin but did not influence P-gp function. The combination of genistein and doxorubicin significantly induced cell cycle arrest and apoptosis. Genistein treatment strongly inhibited HER2/neu but not MDR-1 expression at both the mRNA and protein levels. Therefore, our results demonstrated that genistein combined with doxorubicin had a synergistic effect on MCF-7/Adr cells, and the mechanisms likely involve an increase in the intracellular accumulation of doxorubicin and suppression of HER2/neu expression.
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