title: 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.
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.
authors.affiliation: Department of General Surgery, Huashan Hospital of Fudan University, Shanghai 200040, China Institute of Cancer Metastasis, Fudan University, Shanghai 200040, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of General Surgery, Huashan Hospital of Fudan University, Shanghai 200040, China Institute of Cancer Metastasis, Fudan University, Shanghai 200040, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Lu
authors.affiliation: Department of Stomatology, Huashan Hospital of Fudan University, Shanghai 200040, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Pei
authors.affiliation: Department of General Surgery, Huashan Hospital of Fudan University, Shanghai 200040, China Institute of Cancer Metastasis, Fudan University, Shanghai 200040, China.
authors.forename: Jinhong
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Huashan Hospital of Fudan University, Shanghai 200040, China Institute of Cancer Metastasis, Fudan University, Shanghai 200040, China.
authors.forename: Lunxiu
authors.initials: L
authors.lastname: Qin
authors.affiliation: 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.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Zhu
authors.affiliation: 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.
authors.forename: Huliang
authors.initials: H
authors.lastname: Jia
mesh_terms: D000818:Animals; D001241:Aspirin / Q000737:chemistry*; D001596:Benzylamines; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000378:metabolism*; D000080027:Cyclams; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006571:Heterocyclic Compounds / Q000737:chemistry; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000737:chemistry; D010671:Phenylurea Compounds / Q000737:chemistry*; D019718:Receptors, CXCR4 / Q000378:metabolism; D000077157:Sorafenib; D059016:Tumor Microenvironment
chemical_list: D001596:Benzylamines; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D000080027:Cyclams; D006571:Heterocyclic Compounds; D010671:Phenylurea Compounds; D019718:Receptors, CXCR4; D009536:Niacinamide; D000077157:Sorafenib; D001241:Aspirin; C088327:plerixafor
keywords: SDF1-α; aspirin; hepatocellular carcinoma; sorafenib; tumor invasion and metastasis