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Acta Biochim Biophys Sin (Shanghai). 2015 Dec;47(12):988-96. doi: 10.1093/abbs/gmv112.

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.

Author information

1
Department of General Surgery, Huashan Hospital of Fudan University, Shanghai 200040, China Institute of Cancer Metastasis, Fudan University, Shanghai 200040, China.
2
Department of Stomatology, Huashan Hospital of Fudan University, Shanghai 200040, China.
3
Department of General Surgery, Huashan Hospital of Fudan University, Shanghai 200040, China Institute of Cancer Metastasis, Fudan University, Shanghai 200040, China westoolife@163.com jiahuliang@huashan.org.cn.

Abstract

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-α) expression in paratumor and intratumor tissues, and aspirin attenuates sorafenib-induced increase of SDF1-α expression in paratumor and intratumor tissues. Further studies show that SDF1-α improves cell invasion potential of HCC cells, and that AMD3100, a specific inhibitor of SDF1-α 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-α 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.

KEYWORDS:

SDF1-α; aspirin; hepatocellular carcinoma; sorafenib; tumor invasion and metastasis

PMID:
26607439
DOI:
10.1093/abbs/gmv112
[Indexed for MEDLINE]

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