Journal
EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE
Volume 2019, Issue -, Pages -Publisher
HINDAWI LTD
DOI: 10.1155/2019/9610629
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Funding
- National Nature Science Foundation of China [81503578, 81803934]
- Shanghai Health and Family Planning Commission Research Fund Project [201540036]
- National Nature Science Nurturing Project of Baoshan Branch, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine [GZRPYJJ-201702]
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Background. Formononetin, an active ingredient isolated from the traditional Chinese medicinal herb Astragalus membranaceus, has anticancer and chemoresistance-reducing biological activities. We evaluated the efficacy of formononetin in improving the tumoricidal effect of everolimus by suppressing the mTOR pathway in breast cancer cells. Methods. Cell survival was assessed using an MTT assay. Apoptosis was detected using flow cytometry. Proteins related to the mTOR pathway were detected and assessed using real-time PCR and Western blot analysis. Results. The results showed that formononetin enhances the efficacy of everolimus in suppressing breast cancer cell growth both in vitro and in vivo. The combination of formononetin and everolimus resulted in a 2-fold decrease in tumor volume and a 21.6% decrease in cell survival. The apoptosis ratio in cells treated with formononetin and everolimus increased by 27.9%. Formononetin and everolimus also inhibited the expression of p- mTOR and p-P70S6K and increased the expression of PTEN and p-4EBP-1. Notably, formononetin alone inhibited p-Akt expression but not everolimus. Conclusions. Formononetin enhances the tumoricidal effect of everolimus by inhibiting the activity of Akt.
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