Down-regulation of SDF1-α expression in tumor microenvironment is associated with aspirin-mediated suppression of the pro-metastasis effect of sorafenib in hepatocellular carcinoma
Down-regulation of SDF1-α expression in tumor microenvironment is associated with aspirin-mediated suppression of the pro-metastasis effect of sorafenib in hepatocellular carcinoma
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肿瘤微环境中 SDF1-α 表达的下调与阿司匹林介导的索拉非尼在肝细胞癌中促转移作用的抑制有关。
DOI：
10.1093/abbs/gmv112
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发表时间：
2015-12-01
影响因子：
3.7
通讯作者：
Jia, Huliang
中科院分区：
文献类型：
--
作者：
Lu, Lu;Lu, Ming;Jia, Huliang
索拉非尼被认为是晚期肝细胞癌（HCC）的一线治疗药物。显着延缓肿瘤进展时间；然而，它增加了 HCC 的侵袭和转移潜力。最近的研究表明，阿司匹林可以有效预防和治疗肿瘤，阿司匹林与索拉非尼联合治疗可显着抑制索拉非尼引起的肝内转移。然而，阿司匹林抑制索拉非尼诱导的肝内转移的机制仍不清楚。在这项研究中，我们发现索拉非尼显着增加瘤旁和瘤内组织中基质衍生因子1-α（SDF1-α）的表达，而阿司匹林减弱索拉非尼诱导的瘤旁和瘤内组织中SDF1-α表达的增加。进一步的研究表明，SDF1-α可提高HCC细胞的细胞侵袭能力，而SDF1-α受体CXCR4的特异性抑制剂AMD3100可抑制体内索拉非尼诱导的HCC肝内转移能力的升高。总的来说，这项研究揭示了索拉非尼诱导的瘤旁和瘤内微环境中 SDF1-α 表达的增加受到阿司匹林的抑制，这与阿司匹林介导的对索拉非尼在 HCC 中促转移作用的抑制有关。
Sorafenib is considered to be the first-line therapy for advanced hepatocellular carcinoma (HCC). It significantly delays tumor progression time; however, it increases the invasive and metastatic potential of HCC. Recent studies have shown that aspirin is effective in preventing and treating tumors, and the combination treatment of aspirin and sorafenib significantly suppresses sorafenib-induced intrahepatic metastasis. However, the mechanism through which aspirin suppresses the sorafenib-induced intrahepatic metastasis is still unclear. In this study, we find that sorafenib markedly increases stromal-derived factor 1-alpha (SDF1-alpha) expression in paratumor and intratumor tissues, and aspirin attenuates sorafenib-induced increase of SDF1-alpha expression in paratumor and intratumor tissues. Further studies show that SDF1-alpha improves cell invasion potential of HCC cells, and that AMD3100, a specific inhibitor of SDF1-alpha receptor CXCR4, suppresses the elevated intrahepatic metastatic potential of HCC induced by sorafenib in vivo. Collectively, this study reveals that the sorafenib-induced increase of SDF1-alpha expression in paratumor and intratumor microenvironments is suppressed by aspirin, which is associated with aspirin-mediated suppression of the pro-metastasis effect of sorafenib in HCC.