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雷公藤甲素抑制人神经母细胞瘤细胞的增殖和致瘤性。

Triptolide inhibits cell proliferation and tumorigenicity of human neuroblastoma cells.

作者信息

Yan Xiaomin, Ke Xiao-Xue, Zhao Hailong, Huang Mengying, Hu Renjian, Cui Hongjuan

机构信息

State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716, P.R. China.

出版信息

Mol Med Rep. 2015 Feb;11(2):791-6. doi: 10.3892/mmr.2014.2814. Epub 2014 Oct 29.

DOI:10.3892/mmr.2014.2814
PMID:25354591
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4262511/
Abstract

Triptolide is a diterpene triepoxide, extracted from the Chinese herb Tripterygium wilfordii Hook F, which has been shown to have antitumor activity in a number of cancers. Neuroblastoma is an aggressive extracranial pediatric solid tumor, with significant chemotherapeutic resistance. In this study, triptolide was hypothesized to be a potential therapeutic agent for neuroblastoma. The effects of triptolide on neuroblastoma cell growth and tumor development were investigated. Cell growth and proliferation were evaluated using a cell counting kit‑8 assay and a 5-bromo-2-deoxyuridine staining assay. Cell cycle and apoptosis were detected by flow cytometry. Reverse transcription‑quantitative polymerase chain reaction was conducted to detect the expression levels of the apoptosis‑associated proteins, caspase‑3 and caspase‑9. The tumorigenicity of neuroblastoma cells was assessed by a soft agar clonogenic assay and an in vivo tumorigenic assay. The results demonstrated that exposure of BE(2)‑C human neuroblastoma cells to triptolide resulted in a reduction in cell growth and proliferation, and the induction of cell death and apoptosis, together with cell cycle arrest in the S phase. A soft agar assay indicated that triptolide inhibited the colony‑forming ability of BE(2)‑C neuroblastoma cells. The xenograft experiment showed that triptolide significantly reduced tumor growth and development in vivo. The data suggested that this Chinese herb may be a potential novel chemotherapeutic agent for neuroblastoma.

摘要

雷公藤甲素是一种二萜类三环氧物,从中药雷公藤中提取,已显示在多种癌症中具有抗肿瘤活性。神经母细胞瘤是一种侵袭性的儿童颅外实体瘤,具有显著的化疗耐药性。在本研究中,雷公藤甲素被假设为神经母细胞瘤的一种潜在治疗药物。研究了雷公藤甲素对神经母细胞瘤细胞生长和肿瘤发展的影响。使用细胞计数试剂盒-8检测法和5-溴-2-脱氧尿苷染色检测法评估细胞生长和增殖。通过流式细胞术检测细胞周期和凋亡。进行逆转录-定量聚合酶链反应以检测凋亡相关蛋白caspase-3和caspase-9的表达水平。通过软琼脂克隆形成检测法和体内致瘤检测法评估神经母细胞瘤细胞的致瘤性。结果表明,将BE(2)-C人神经母细胞瘤细胞暴露于雷公藤甲素会导致细胞生长和增殖减少,诱导细胞死亡和凋亡,并使细胞周期停滞于S期。软琼脂检测表明,雷公藤甲素抑制BE(2)-C神经母细胞瘤细胞的集落形成能力。异种移植实验表明,雷公藤甲素在体内显著降低肿瘤生长和发展。数据表明,这种中药可能是神经母细胞瘤一种潜在的新型化疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3eb9/4262511/65400b747dff/MMR-11-02-0791-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3eb9/4262511/2312e13c0241/MMR-11-02-0791-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3eb9/4262511/a8f28121c6c5/MMR-11-02-0791-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3eb9/4262511/88a13cc20ab2/MMR-11-02-0791-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3eb9/4262511/70366d3da962/MMR-11-02-0791-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3eb9/4262511/398f9f64d887/MMR-11-02-0791-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3eb9/4262511/65400b747dff/MMR-11-02-0791-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3eb9/4262511/2312e13c0241/MMR-11-02-0791-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3eb9/4262511/a8f28121c6c5/MMR-11-02-0791-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3eb9/4262511/88a13cc20ab2/MMR-11-02-0791-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3eb9/4262511/70366d3da962/MMR-11-02-0791-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3eb9/4262511/398f9f64d887/MMR-11-02-0791-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3eb9/4262511/65400b747dff/MMR-11-02-0791-g05.jpg

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本文引用的文献

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Planta Med. 2014 Mar;80(4):255-61. doi: 10.1055/s-0033-1360315. Epub 2014 Feb 7.
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Triptolide induces apoptosis through the SERCA 3 upregulation in PC12 cells.雷公藤甲素通过上调PC12细胞中的肌浆网钙ATP酶3诱导细胞凋亡。
Gen Physiol Biophys. 2014;33(1):137-44. doi: 10.4149/gpb_2014004. Epub 2014 Jan 22.
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Low-dose of multi-glycoside of Tripterygium wilfordii Hook. f., a natural regulator of TGF-β1/Smad signaling activity improves adriamycin-induced glomerulosclerosis in vivo.
基于氢核磁共振的代谢组学揭示雷公藤内酯醇对荷CT26肿瘤BALB/c小鼠的抗肿瘤机制。
Front Pharmacol. 2019 Oct 11;10:1175. doi: 10.3389/fphar.2019.01175. eCollection 2019.
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Triptolide Decreases Cell Proliferation and Induces Cell Death in Triple Negative MDA-MB-231 Breast Cancer Cells.雷公藤内酯醇可降低三阴性 MDA-MB-231 乳腺癌细胞的增殖并诱导其死亡。
Biomolecules. 2018 Dec 5;8(4):163. doi: 10.3390/biom8040163.
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Triptolide inhibits Epstein-Barr nuclear antigen 1 expression by increasing sensitivity of mitochondria apoptosis of nasopharyngeal carcinoma cells.雷公藤红素通过增加鼻咽癌细胞线粒体凋亡的敏感性来抑制 Epstein-Barr 核抗原 1 的表达。
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Cochrane Database Syst Rev. 2013 Aug 11(8):CD008568. doi: 10.1002/14651858.CD008568.pub2.