Efficacy and mechanism of action of Deguelin in suppressing metastasis of 4T1 cells.
Efficacy and mechanism of action of Deguelin in suppressing metastasis of 4T1 cells.
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DOI：
10.1007/s10585-013-9585-6
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发表时间：
2013-10
影响因子：
4
通讯作者：
Mehta RG
中科院分区：
文献类型：
--
作者：
Mehta RR;Katta H;Kalra A;Patel R;Gupta A;Alimirah F;Murillo G;Peng X;Unni A;Muzzio M;Mehta RG
乳腺癌患者与癌症相关的死亡是由于疾病转移造成的。鼠4 T1细胞（从6-硫鸟嘌呤抗性肿瘤发展而来的鼠乳腺癌细胞系）为转移相关研究提供了极好的研究工具，因为这些细胞具有高度侵袭性并且容易转移到肺。在这项研究中，我们确定鱼藤素对4 T1细胞的体内/体外生长和转移的影响。鱼藤素对4 T1细胞的体外生长有明显的抑制作用，并呈时间和剂量依赖性，同时伴有细胞核PCNA免疫染色的减弱。在用鱼藤素处理的细胞中，观察到核c-Met及其下游靶点如p-ERK和p-AKT的表达减少。鱼藤素减少4 T1细胞中的细胞迁移，如通过划痕试验所确定的。鱼藤素+ ERK或PI 3 K/AKT抑制剂的组合处理对细胞迁移没有额外的影响。这些结果表明鱼藤素对细胞迁移的作用可能是通过AKT和ERK信号通路介导的。在体内，鱼藤素处理显著抑制4 T1细胞的生长。鱼藤素也减少了33%的转移性肺病变的发生时，细胞静脉注射到Balb/c雌性小鼠。溶媒处理对照组和鱼藤素处理组动物之间的体重以及肝脏和脾脏重量无差异，表明鱼藤素在本研究中使用的剂量下无毒。这些结果为开发鱼藤素作为三阴性乳腺癌患者的化疗剂提供了理论基础。
Cancer related deaths in breast cancer patients are due to metastasis of the disease. Murine 4T1 cells (Murine mammary cancer cell line developed from 6-thioguanine resistant tumor) provide an excellent research tool for metastasis related studies because these cells are highly aggressive and readily metastasize to the lungs. In this study we determined the effect of Deguelin on in vivo/vitro growth and metastasis of 4T1 cells. Deguelin inhibited the in vitro growth of 4T1 cells in a time and dose dependent manner accompanied with reduced nuclear PCNA immunostaining. In cells treated with Deguelin, reduced expression of nuclear c-Met, and its downstream targets such p-ERK and p-AKT was observed. Deguelin reduced the cell migration in 4T1 cells as determined by scratch wound assay. Combined treatment with Deguelin + ERK or PI3K/AKT inhibitor had no additional effect on cell migration. These results indicated that the action of Deguelin on cell migration may be mediated by AKT and ERK mediated signaling pathways. In vivo, Deguelin treatment significantly inhibited growth of 4T1 cells. Deguelin also reduced the occurrence of metastatic lung lesions by 33% when cells were injected intravenously into Balb/c female mice. There was no difference in the body weight as well as liver and spleen weights between vehicle treated control and Deguelin treated animals indicating that Deguelin was nontoxic at the dose used in the present study. These results provide rationale for developing Deguelin as a chemotherapeutic agent for triple negative breast cancer patients.
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DOI：
10.1158/1078-0432.ccr-08-3252
发表时间：
2009-06-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Knowles LM;Stabile LP;Egloff AM;Rothstein ME;Thomas SM;Gubish CT;Lerner EC;Seethala RR;Suzuki S;Quesnelle KM;Morgan S;Ferris RL;Grandis JR;Siegfried JM
通讯作者：
Siegfried JM
影响因子：
4.1
作者：
Caboni, P;Sherer, TB;Casida, JE
通讯作者：
Casida, JE
影响因子：
4.7
作者：
Kermorgant, S;Aparicio, T;Lehy, T
通讯作者：
Lehy, T
影响因子：
11.5
作者：
Lee, HY;Suh, YA;Kurie, JM
通讯作者：
Kurie, JM
影响因子：
6.2
作者：
Bhargava, Rohit;Beriwal, Sushil;Ahrendt, Gretchen M.
通讯作者：
Ahrendt, Gretchen M.