ERK inhibition sensitizes cancer cells to oleanolic acid-induced apoptosis through ERK/Nrf2/ROS pathway
ERK inhibition sensitizes cancer cells to oleanolic acid-induced apoptosis through ERK/Nrf2/ROS pathway
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ERK 抑制通过 ERK/Nrf2/ROS 途径使癌细胞对齐墩果酸诱导的细胞凋亡敏感
DOI：
10.1007/s13277-015-4668-4
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发表时间：
2016-06-01
期刊：
影响因子：
--
通讯作者：
Liang, Hui
中科院分区：
文献类型：
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作者：
Liu, Jia;Ma, Leina;Liang, Hui
油酸（OA）是一种天然三萜类化合物，广泛分布于食药用植物中。OA主要通过诱导细胞凋亡对广泛的癌细胞发挥抗肿瘤活性。失调的ERK信号传导在癌症的生物学中非常复杂，例如转移、增殖和存活，并且它可以被各种刺激激活。在本研究中，我们发现OA诱导了癌细胞中ERK的激活。ERK的激活削弱了OA诱导的细胞凋亡。通过U0126或siRNA阻断ERK活化能够增强OA对癌细胞的促凋亡活性。OA显示促进癌细胞中ERK依赖性Nrf2表达，反过来，Nrf2表达能够抑制OA诱导的ROS产生。阻断Nrf2表达能够增加癌细胞中的ROS水平和凋亡死亡。总之，我们提供的证据表明，ERK激活是一种潜在的机制，癌细胞抵抗OA诱导的凋亡和靶向ERK是一个有前途的策略，以提高OA的抗肿瘤疗效。
Oleanolic acid (OA) is a natural triterpenoid that is widely distributed in edible and medicinal plants. OA exerts anti-tumor activity on a wide range of cancer cells primarily through inducing apoptosis. Dysregulated ERK signaling is closely complicated in the biology of cancer, such as metastasis, proliferation, and survival, and it can be activated by various stimuli. In this study, we found that OA induced the activation of ERK in cancer cells. ERK activation compromised the apoptosis induced by OA. Blocking ERK activation by U0126 or siRNAs was able to potentiate the pro-apoptotic activity of OA on cancer cells. OA was shown to promote ERK-dependent Nrf2 expression in cancer cells, and in turn, Nrf2 expression was able to suppress OA-induced ROS generation. Blockade of Nrf2 expression was able to increase ROS levels and apoptotic death in cancer cells. In conclusion, we provided evidences that ERK activation is a mechanism underlying the resistance of cancer cells to OA-induced apoptosis and targeting ERK is a promising strategy to enhance the anti-tumor efficacy of OA.