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雷公藤甲素调节丝裂原活化蛋白激酶信号通路并通过内质网应激介导的细胞凋亡诱导对人骨肉瘤细胞发挥抗癌作用。

Triptonide Modulates MAPK Signaling Pathways and Exerts Anticancer Effects via ER Stress-Mediated Apoptosis Induction in Human Osteosarcoma Cells.

作者信息

Zheng Liyun, Fang Shiji, Hui Junguo, Rajamanickam Vinothkumar, Chen Minjiang, Weng Qiaoyou, Wu Xulu, Zhao Zhongwei, Ji Jiansong

机构信息

Interventional Diagnosis and Treatment Center, Lishui Hospital of Zhejiang University, Lishui, Zhejiang 323000, People's Republic of China.

Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Lishui Hospital of Zhejiang University, Lishui, Zhejiang 323000, People's Republic of China.

出版信息

Cancer Manag Res. 2020 Jul 17;12:5919-5929. doi: 10.2147/CMAR.S258203. eCollection 2020.

DOI:10.2147/CMAR.S258203
PMID:32765093
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7373419/
Abstract

BACKGROUND

Osteosarcoma (OS) is the most common primary malignancy arise from bone and is one of the causes of cancer-related deaths. Triptonide (TN), a diterpenoid epoxide presented in , is shown to possess a broad spectrum of biological properties.

METHODS

In this study, we investigate the growth inhibitory effect of TN against human OS cells and its underlying molecular mechanism of action.

RESULTS

Findings of our in vitro study revealed that TN exhibited a dose-dependent cytotoxic effect in MG63 and U-2OS cells. ROS-mediated cytotoxic effect was achieved in OS cells treated with TN which was reversed upon NAC treatment. Significantly, increased expression of PERK, p-EIF2, GRP78, ATF4 and CHOP in TN-treated OS cells unfolds the molecular mechanism of TN targets ER stress-mediated apoptosis. Modulation of ERK MAPK pathway was also observed as evidenced by the increased phosphorylation of ERK (p-ERK) and p-p38 in TN-treated OS cells.

CONCLUSION

Altogether, the outcome of the study for the first time revealed that TN exhibited its potential chemotherapeutic effects through ROS-mediated ER stress-induced apoptosis via p38 and ERK MAPK signaling pathways.

摘要

背景

骨肉瘤（OS）是最常见的原发性骨恶性肿瘤，也是癌症相关死亡的原因之一。雷公藤内酯醇（TN）是一种存在于[具体来源未给出]中的二萜环氧化物，具有广泛的生物学特性。

方法

在本研究中，我们研究了TN对人OS细胞的生长抑制作用及其潜在的分子作用机制。

结果

我们的体外研究结果表明，TN在MG63和U-2OS细胞中表现出剂量依赖性的细胞毒性作用。在用TN处理的OS细胞中实现了ROS介导的细胞毒性作用，而NAC处理后这种作用被逆转。值得注意的是，在经TN处理的OS细胞中，PERK、p-EIF2、GRP78、ATF4和CHOP的表达增加，揭示了TN靶向内质网应激介导的细胞凋亡的分子机制。在用TN处理的OS细胞中，ERK（p-ERK）和p-p38磷酸化增加，也证明了ERK MAPK途径的调节。

结论

总之，该研究结果首次表明，TN通过ROS介导的内质网应激诱导的细胞凋亡，经由p38和ERK MAPK信号通路发挥其潜在的化疗作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbd6/7373419/3d11f6a1cebb/CMAR-12-5919-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbd6/7373419/3d11f6a1cebb/CMAR-12-5919-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbd6/7373419/3d11f6a1cebb/CMAR-12-5919-g0001.jpg

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