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阿司匹林在间变性甲状腺癌中的潜在治疗价值。

The Potential Therapeutic Value of Aspirin in Anaplastic Thyroid Cancer.

作者信息

Baldini Enke, Cardarelli Silvia, Lori Eleonora, Bonati Elena, Gagliardi Federica, Pironi Daniele, Fallahi Poupak, Antonelli Alessandro, D'Andrea Vito, Ulisse Salvatore, Sorrenti Salvatore

机构信息

Department of Surgery, "Sapienza" University of Rome, 00161 Rome, Italy.

General Surgery Unit, Department of Medicine and Surgery, Parma University Hospital, 43126 Parma, Italy.

出版信息

Cancers (Basel). 2024 Dec 17;16(24):4203. doi: 10.3390/cancers16244203.

DOI:10.3390/cancers16244203
PMID:39766102
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11674608/
Abstract

several experimental findings and epidemiological observations indicated that aspirin/acetylsalicylic acid (ASA) may be endowed with anticancer effects against a variety of human malignancies, including thyroid carcinomas. Among these, undifferentiated/anaplastic thyroid carcinoma (ATC) is one of the most aggressive and lethal human cancers, refractory to all currently available therapies. we here evaluated in a preclinical setting the effects of ASA on a panel of three ATC-derived cell lines: the CAL-62, the 8305C, and the 8505C. the data obtained demonstrated the ability of ASA to inhibit, in a dose- and time-dependent manner, the proliferation of all ATC cell lines investigated, with IC values comprised between 2.0 and 4.3 mM. Cell growth was restrained with the same efficacy when the ASA treatment was applied to three-dimensional soft-agar cultures. In addition, ASA significantly reduced migration and invasion in two of the three ATC cell lines. We finally investigated the effects of ASA on the MAPK and PI3K/Akt signaling pathways, which are often altered in ATC. The results showed that the phosphorylation status of the Akt1/2/3 kinases was significantly reduced following ASA treatment, while ERK1/2 phosphorylation was either unaffected or slightly upregulated. our findings support epidemiological evidence on the anticancer potential of ASA. On this basis, further investigations should be carried out to assess the usefulness of ASA as adjuvant therapy in patients affected by ATC.

摘要

多项实验结果和流行病学观察表明,阿司匹林/乙酰水杨酸(ASA)可能具有针对多种人类恶性肿瘤(包括甲状腺癌)的抗癌作用。其中,未分化/间变性甲状腺癌(ATC)是最具侵袭性和致命性的人类癌症之一,对目前所有可用的治疗均具有抗性。我们在此在临床前环境中评估了ASA对一组三种源自ATC的细胞系的影响:CAL-62、8305C和8505C。获得的数据表明,ASA能够以剂量和时间依赖性方式抑制所有所研究的ATC细胞系的增殖,IC值在2.0至4.3 mM之间。当将ASA处理应用于三维软琼脂培养时,细胞生长受到同样有效的抑制。此外,ASA显著降低了三种ATC细胞系中的两种的迁移和侵袭。我们最终研究了ASA对MAPK和PI3K/Akt信号通路的影响,这些信号通路在ATC中经常发生改变。结果表明,ASA处理后Akt1/2/3激酶的磷酸化状态显著降低,而ERK1/2磷酸化要么未受影响,要么略有上调上调。我们的研究结果支持了关于ASA抗癌潜力的流行病学证据。在此基础上,应进一步开展研究,以评估ASA作为ATC患者辅助治疗的有效性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7547/11674608/fa9b793d1605/cancers-16-04203-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7547/11674608/fe33aa06f231/cancers-16-04203-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7547/11674608/0a2cec5c4c62/cancers-16-04203-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7547/11674608/df9a1b4d2032/cancers-16-04203-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7547/11674608/a94413624c9d/cancers-16-04203-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7547/11674608/53331b6063d2/cancers-16-04203-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7547/11674608/fddb50991f7c/cancers-16-04203-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7547/11674608/fa9b793d1605/cancers-16-04203-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7547/11674608/fe33aa06f231/cancers-16-04203-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7547/11674608/0a2cec5c4c62/cancers-16-04203-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7547/11674608/df9a1b4d2032/cancers-16-04203-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7547/11674608/a94413624c9d/cancers-16-04203-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7547/11674608/53331b6063d2/cancers-16-04203-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7547/11674608/fddb50991f7c/cancers-16-04203-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7547/11674608/fa9b793d1605/cancers-16-04203-g007.jpg

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本文引用的文献

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Pharmacokinetic Profile and Comparative Bioavailability of an Oral Fixed-Dose Combination of Metformin and Acetylsalicylic Acid (Aspirin).二甲双胍与乙酰水杨酸(阿司匹林)口服固定剂量复方制剂的药代动力学特征及相对生物利用度
Clin Pharmacol Drug Dev. 2024 Nov;13(11):1245-1252. doi: 10.1002/cpdd.1450. Epub 2024 Jul 22.
2
The 125th Anniversary of Aspirin-The Story Continues.阿司匹林问世125周年——故事仍在继续。
Pharmaceuticals (Basel). 2024 Mar 28;17(4):437. doi: 10.3390/ph17040437.
3
Evaluation of the Therapeutic Effects of Harmine on Anaplastic Thyroid Cancer Cells.
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Int J Mol Sci. 2024 Jan 17;25(2):1121. doi: 10.3390/ijms25021121.
4
Using aspirin to prevent and treat cancer.使用阿司匹林预防和治疗癌症。
Inflammopharmacology. 2024 Feb;32(1):903-908. doi: 10.1007/s10787-023-01346-2. Epub 2023 Dec 8.
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Aspirin and cancer treatment: systematic reviews and meta-analyses of evidence: for and against.阿司匹林与癌症治疗:系统评价和荟萃分析证据:支持与反对。
Br J Cancer. 2024 Jan;130(1):3-8. doi: 10.1038/s41416-023-02506-5. Epub 2023 Nov 29.
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NF-κB signaling activation and roles in thyroid cancers: implication of MAP3K14/NIK.NF-κB信号通路激活及其在甲状腺癌中的作用:MAP3K14/NIK的影响
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Long-term aspirin use and cancer risk: a 20-year cohort study.长期服用阿司匹林与癌症风险:一项 20 年的队列研究。
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