Background: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.Methods: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.Results: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 IC50values 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.Conclusions: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.
背景：多项实验发现与流行病学观察表明，阿司匹林/乙酰水杨酸（ASA）可能对包括甲状腺癌在内的多种人类恶性肿瘤具有抗癌作用。其中，未分化/间变性甲状腺癌（ATC）作为最具侵袭性和致死性的人类癌症之一，对当前所有可用疗法均表现出耐药性。 方法：本研究在临床前环境中评估了ASA对三种ATC衍生细胞系（CAL-62、8305C和8505C）的作用效果。 结果：实验数据表明，ASA能以剂量和时间依赖性方式抑制所有受试ATC细胞系的增殖，其半数抑制浓度（IC50）介于2.0至4.3 mM之间。在三维软琼脂培养体系中，ASA处理同样能有效抑制细胞生长。此外，ASA显著降低了三种ATC细胞系中两种细胞的迁移和侵袭能力。最后，我们研究了ASA对MAPK和PI3K/Akt信号通路的影响——这两条通路在ATC中常发生异常激活。结果显示ASA处理后Akt1/2/3激酶的磷酸化水平显著降低，而ERK1/2磷酸化水平未受影响或轻微上调。 结论：本研究为ASA抗癌潜能的流行病学证据提供了实验支持。基于此，有必要开展进一步研究以评估ASA作为ATC患者辅助治疗方案的临床应用价值。
The Potential Therapeutic Value of Aspirin in Anaplastic Thyroid Cancer
肿瘤(癌症)患者之家