IGF1R tyrosine kinase inhibitor enhances the cytotoxic effect of methyl jasmonate in endometrial cancer
IGF1R tyrosine kinase inhibitor enhances the cytotoxic effect of methyl jasmonate in endometrial cancer
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DOI：
10.1016/j.canlet.2014.06.013
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发表时间：
2014-10-01
期刊：
影响因子：
9.7
通讯作者：
Werner, Haim
中科院分区：
文献类型：
--
作者：
Bruchim, Ilan;Sarfstein, Rive;Werner, Haim
本研究评估了茉莉酸甲酯（MJ）在子宫内膜癌细胞中的细胞毒活性，并验证了MJ在这些细胞系中的凋亡和抗增殖作用可以通过共同靶向胰岛素样生长因子-1受体（IGF1R）信号通路而增强的假设。MJ对所有细胞系均有明显的促凋亡作用和毒性。MJ联合NVP-AEW541（一种选择性IGF1R酪氨酸激酶抑制剂）显著增加细胞毒性。MJ降低了IGF1R的磷酸化水平，但增强了AKT的磷酸化水平，消除了IGF1的抗凋亡作用。这些发现表明IGF1R抑制剂和MJ联合使用可能是治疗子宫内膜癌的一种有吸引力的方式。2014爱思唯尔爱尔兰有限公司版权所有。
The present study evaluated the cytotoxic activity of methyl jasmonate (MJ) in endometrial cancer cells and examined the hypothesis that the apoptotic and anti-proliferative actions of MJ in these cell lines can be enhanced by co-targeting the insulin-like growth factor-1 receptor (IGF1R) signaling pathway. MJ had a potent pro-apoptotic effect and exhibited significant toxicity in all cell lines tested. MJ in combination with NVP-AEW541, a selective IGF1R tyrosine kinase inhibitor, had significantly increased cytotoxicity. MJ decreased IGF1R phosphorylation, however, it enhanced AKT phosphorylation and abolished the anti-apoptotic effect of IGF1. These findings suggest that combined IGF1R inhibitor and MJ administration may constitute an attractive modality for treating endometrial cancer. (C) 2014 Elsevier Ireland Ltd. All rights reserved.