期刊
ONCOTARGET
卷 6, 期 28, 页码 25281-25294出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.4634
关键词
ovarian cancer; anti-cancer agent; isoflavone analog; PI3K/AKT inhibition; cytotoxicity
资金
- National Natural Science Foundation of China [81071839, 81171911, 81372797, 91129721]
- Shanghai Committee of Science and Technology of China [14431900600]
- China Postdoctoral Science Foundation [2013M531126]
- Shanghai Pujiang Program from the Shanghai Municipal Government of China [11PJ1402200]
- Ministry of Education of China [20120071110079]
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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