RY-2f, an isoflavone analog, overcomes cisplatin resistance to inhibit ovarian tumorigenesis via targeting the PI3K/AKT/mTOR signaling pathway

Oncotarget
Mingming LiuQian Zhang

Abstract

Ovarian cancer remains the leading cause of death in gynecologic malignancies partially because of resistance to chemotherapy. In the present study, we show that RY-2f, a chemically synthesized isoflavone analog, inhibited ovarian cancer cell proliferation, blocked cell cycle in G2/M phase and induced cellular apoptosis through up-regulation of p21, cyclin B1, Bax, Bad and cleaved-PARP, and suppression of cyclin A, CDK2 and Bcl-2. We also show that RY-2f could increase the chemotherapeutic efficacy of cisplatin as tested by cell proliferation and colony formation assays, indicating a synergistic effect of RY-2f and cisplatin. Mechanistic study revealed that RY-2f exerted the anti-tumor activities mainly through suppression of the PI3K/AKT/mTOR signaling. Finally, in vivo studies showed that RY-2f blocked the A2780-induced xenograft tumor growth without detectable toxicity in the animals at the therapeutic doses, and whereas RY-2f re-sensitized the cisplatin resistant cell line A2780/CDDP induced xenograft tumor to cisplatin treatment. Thus, RY-2f may be developed as a potential therapeutic agent to treat ovarian cancer.

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Citations

Feb 6, 2020·Mass Spectrometry Reviews·Na Li, Xianquan Zhan
Mar 5, 2016·Journal of Experimental & Clinical Cancer Research : CR·Rui YuQi Ma
Jan 14, 2017·International Journal of Molecular Sciences·Tao TaoJunqi He
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Jun 8, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yi YangChengxin Li
Nov 8, 2017·Journal of Agricultural and Food Chemistry·Hui-Ying LiNan Zheng

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Methods Mentioned

BETA
flow cytometry
xenograft
protein kinase assay
transfection
protein assay
electrophoresis

Software Mentioned

Multicycle AV
Graph Pad Prism
CompuSyn

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