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Formononetin sensitizes glioma cells to doxorubicin through preventing EMT via inhibition of histone deacetylase 5
Authors:Quan Liu  Yan Sun  Jie-Min Zheng  Xian-Lei Yan  Hong-Mou Chen  Jia-Kang Chen  He-Qing Huang
Affiliation:1.Department of Neurosurgery, The Fourth Affiliated Hospital Guangxi Medical University, Liuzhou 545005, Guangxi, China;2.Department of Scientific Research and Education, The Fourth Affiliated Hospital Guangxi Medical University, Liuzhou 545005, Guangxi, China
Abstract:Chemoresistance is a major obstacle to successful chemotherapy for glioma. Formononetin is a novel herbal isoflavonoid isolated from Astragalus membranaceus and possesses antitumorigenic properties. In the present study, we investigated the anti-proliferative effects of formononetin on human glioma cells, and further elucidated the molecular mechanism underlying the anti-tumor property. We found that formononetin enhanced doxorubicin cytotoxicity in glioma cells. Combined treatment with formononetin reversed the doxorubicin-induced epithelial-mesenchymal transition (EMT) in tumor cells. Moreover, we found that formononetin treatment significantly decreased the expression of HDAC5. Overexpression of HDAC5 diminished the suppressive effects of formononetin on glioma cell viability. Furthermore, knockdown of HDAC5 by siRNA inhibited the doxorubicin-induced EMT in glioma cells. Taken together, these results demonstrated that formononetin-combined therapy may enhance the therapeutic efficacy of doxorubicin in glioma cells by preventing EMT through inhibition of HDAC5.
Keywords:Glioma   epithelial-mesenchymal transition   HDAC5   combination treatment
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