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二eckol通过抑制PI3K/AKT/mTOR信号通路在人骨肉瘤(MG-63)细胞中发挥抗癌活性。

Dieckol exerts anticancer activity in human osteosarcoma (MG-63) cells through the inhibition of PI3K/AKT/mTOR signaling pathway.

作者信息

Zhang Shouqiang, Ren Hui, Sun Hanting, Cao Songhua

机构信息

Department of Orthopaedic & Trauma Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, No. 247 Beiyuan Street, Jinan, Shandong 250033, China.

Department of Cardiothoracic Surgery, Xinwen Mining Group Central Hospital, Xintai City, Shandong Province 271200, China.

出版信息

Saudi J Biol Sci. 2021 Sep;28(9):4908-4915. doi: 10.1016/j.sjbs.2021.07.019. Epub 2021 Jul 12.

Abstract

BACKGROUND

Osteosarcoma (OS) is the most common malignant bone cancer with more metastasis and increased occurrence in children and teen-agers and being responsible for more number of morbidity and mortality worldwide.

OBJECTIVE

The current exploration was planned study the anticancer actions of dieckol against human OS MG-63 cells via PI3K/AKT/mTOR signaling inhibition.

METHODOLOGY

The cytotoxicity of dieckol was scrutinized by MTT assay. Effects of dieckol on the ROS accumulation, apoptotic cell death, and MMP level in the MG-63 cells were studied by respective fluorescence staining assays. The levels of proliferative, inflammatory, and apoptotic markers in the dieckol treated MG-63 cells were scrutinized by marker specific kits. The expressions of PI3K, AKT, and mTOR was assayed by RT-PCR.

RESULTS

The MTT assay revealed that the dieckol dose dependently prevented MG-63 cells viability and the IC50 was found at 15 µM. Dieckol treatment effectively reduced the MMP level and improved the ROS generation and apoptosis in MG-63 cells. Dieckol also regulated the proliferative (cyclin D1), inflammatory (COX-2, IL-6, TNF-α, and NF-κB), and apoptotic (caspase-3, Bax, Bcl-2) markers in the MG-63 cells. The PI3K/AKT/mTOR signaling in the MG-63 cells were effectively inhibited by the dieckol treatment.

CONCLUSION

In conclusion, our findings from this study recommends that the dieckol could be a talented anticancer candidate for the OS management in the future.

摘要

背景

骨肉瘤(OS)是最常见的恶性骨癌,在儿童和青少年中转移更多、发病率增加,在全球范围内导致更多的发病和死亡。

目的

本研究旨在探讨二eckol通过抑制PI3K/AKT/mTOR信号通路对人骨肉瘤MG-63细胞的抗癌作用。

方法

采用MTT法检测二eckol的细胞毒性。通过各自的荧光染色试验研究二eckol对MG-63细胞中ROS积累、凋亡细胞死亡和MMP水平的影响。用标记特异性试剂盒检测二eckol处理的MG-63细胞中增殖、炎症和凋亡标记物的水平。通过RT-PCR检测PI3K、AKT和mTOR的表达。

结果

MTT试验显示,二eckol剂量依赖性地抑制MG-63细胞活力,IC50为15μM。二eckol处理有效降低了MG-63细胞的MMP水平,提高了ROS生成和凋亡。二eckol还调节了MG-63细胞中的增殖(细胞周期蛋白D1)、炎症(COX-2、IL-6、TNF-α和NF-κB)和凋亡(半胱天冬酶-3、Bax、Bcl-2)标记物。二eckol处理有效抑制了MG-63细胞中的PI3K/AKT/mTOR信号通路。

结论

总之,我们的研究结果表明,二eckol可能是未来骨肉瘤治疗中一种有潜力的抗癌候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/706f/8381078/a00673dd0dbf/gr1.jpg

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