Deguelin action involves c-Met and EGFR signaling pathways in triple negative breast cancer cells.
Deguelin action involves c-Met and EGFR signaling pathways in triple negative breast cancer cells.
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DOI：
10.1371/journal.pone.0065113
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Mehta RG
中科院分区：
文献类型：
--
作者：
Mehta R;Katta H;Alimirah F;Patel R;Murillo G;Peng X;Muzzio M;Mehta RG
用抗雌激素和芳香酶抑制剂或赫赛汀治疗乳腺癌患者分别在类固醇受体阳性或Her-2+乳腺癌中显示出显著的成功。然而，雌激素、孕激素受体和HER 2/neu阴性状态的乳腺癌患者的治疗选择有限。因此，寻找合适的治疗方案，这些三阴性乳腺癌（TNBC）已成为许多实验室的主要研究重点。最近，从非洲植物Mundulea sericea（Leguminossae）中分离的天然产物Deguelin在包括乳腺癌在内的各种癌症中显示出抗增殖作用，以及对致癌物诱导的实验性癌症的化学预防活性。在这份报告中，我们评估了鱼藤素在三阴性乳腺癌细胞系中的功效和作用机制。鱼藤素在体外对MDA-MB-231、MDA-MB-468、BT-549和BT-20细胞的生长有抑制作用，并呈剂量和时间依赖性。鱼藤素（2或4毫克/公斤体重），当腹腔注射，减少在裸鼠皮下移植的MDA-MB-231细胞的体内肿瘤生长。此外，每日观察活动性、摄食量和饮水量以及研究结束时与对照动物的体重和其他内脏器官重量比较，证明其无毒。Western blot分析和免疫组化研究表明鱼藤素的作用可能是通过下调其下游靶点p-STAT 3、c-Myc、Survivin，通过EGFR-PAKT/c-Met p-ERK和NF-κB介导的。这些结果表明鱼藤素可能对TNBC患者的治疗具有显著的治疗价值。
Treatment of breast cancer patients with antiestrogens and aromatase inhibitor(s) or Herceptin have shown significant success in steroid receptor positive or Her-2+ breast cancers respectively. However, choice of treatments for breast cancer patients with negative status for estrogen, progesterone receptors and HER2/neu is limited. As a result, search for appropriate therapy regimen for these triple negative breast cancers (TNBC) has become a major focus of investigations for many laboratories. Recently, Deguelin, a natural product isolated from African plant Mundulea sericea (Leguminossae) has shown both antiproliferative actions in various cancers including breast as well as chemoprenventive activity against carcinogen induced experimental cancers. In this report we evaluated efficacy and mechanism of action of Deguelin in triple negative breast cancer cell lines. In vitro, Deguelin in a dose and time dependent manner inhibited the growth of MDA-MB-231, MDA-MB-468, BT-549 and BT-20 cells. Deguelin (2 or 4 mg/kg body weight), when injected intraperitoneally, reduced the in vivo tumor growth of MDA-MB-231 cells transplanted subcutaneously in athymic mice. Moreover it was nontoxic as evident from daily observations on mobility, food and water consumption and comparison of bodyweight and other visceral organ weights with those in control animals at the termination of the study. The western blot analyses and immunostaining studies indicated that the deguelin effects may be mediated through EGFR-PAKT/c-Met p-ERK and NF-κB by down regulating their downstream targets such as p-STAT3, c-Myc, Survivin. These results suggest that Deguelin may have a significant therapeutic value for the treatment of TNBC patients.
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影响因子：
1.3
作者：
Griffiths, Carrie L;Olin, Jacqueline L
通讯作者：
Olin, Jacqueline L
影响因子：
4.1
作者：
Caboni, P;Sherer, TB;Casida, JE
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Casida, JE
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3.3
作者：
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Mehta, Rajendra G.
影响因子：
50.5
作者：
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Zielinski, C. C.
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作者：
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