Blockage of CXCR2 suppresses tumor growth of intrahepatic cholangiocellular carcinoma
Blockage of CXCR2 suppresses tumor growth of intrahepatic cholangiocellular carcinoma
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DOI：
10.1016/j.surg.2013.12.037
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发表时间：
2014-04-01
期刊：
影响因子：
3.8
通讯作者：
Fujimoto, Jiro
中科院分区：
文献类型：
--
作者：
Sueoka, Hideaki;Hirano, Tadamichi;Fujimoto, Jiro
背景/目标。手术切除是治疗肝内胆管细胞癌（ICC）的唯一方法，但其预后极差。迫切需要一种新的治疗方法。CXC趋化因子受体2（CXCR 2）与人类肿瘤的发生和转移有关。在这项研究中，我们研究了通过阻断CXCR 2来抑制ICC生长的效果。使用人ICC细胞系RBE和SSP 25估计CXCR 2的作用。使用CXCR 2小干扰RNA（siRNA）和拮抗剂（SB 225002）来阻断CXCR 2。进行增殖测定、迁移测定和侵袭测定以确认阻断CXCR 2的抑制作用。在无胸腺裸鼠中建立皮下SSP 25肿瘤，并给予小鼠SB 225002。采用免疫组化法检测34例ICC中CXCR 2的表达。我们研究了CXCR 2表达与ICC预后的关系。结果。ICC中CXCR 2表达较高的患者预后显著较差（P = .004）。CXCR 2 siRNA处理显着抑制了RBE和SSP 25中CXCR 2的表达。与对照组相比，CXCR 2 siRNA和SB 225002均显著抑制细胞增殖、迁移和侵袭。SB 225002还抑制皮下移植瘤的生长（P = .02）。我们的结果表明，阻断CXCR 2明显抑制了ICC的发展。阻断CXCR 2可能是一种有前途的ICC治疗方法。
Background/Aims. Complete operative resection is the only approach to cure for intrahepatic cholangiocellular carcinoma (ICC), but the disease's prognosis is notably poor. A novel therapeutic approach is urgently required. CXC chemokine receptor 2 (CXCR2) has been associated with tumorigenesis and metastasis in human cancers. In this study, we investigated the suppressive effect of ICC growth by blocking CXCR2.Material and methods. The role of CXCR2 was estimated using the human ICC cell lines, RBE and SSP25. CXCR2 small interfering RNA (siRNA) and an antagonist (SB225002) were used to block CXCR2. Proliferation assays, migration assays, and invasion assays were performed to confirm the suppressive effect of blocking CXCR2. Subcutaneous SSP25 tumors were established in athymic nude mice, and the mice were given SB225002. The expression of CXCR2 in ICC was determined by immunohistochemical staining of 34 ICC specimens. We investigated the relationship between CXCR2 expression and prognosis in ICC.Results. The prognosis of patients who had higher CXCR2 expression in ICC was significantly poor (P = .004). CXCR2 siRNA treatment significantly suppressed CXCR2 expression in both RBE and SSP25. Cell proliferation, migration, and invasion were significantly suppressed by both CXCR2 siRNA and SB225002 compared with the control group. SB225002 also suppressed the growth of transplanted subcutaneous tumors (P = .02)Conclusion. Our results demonstrated that blocking CXCR2 clearly suppressed the development of ICC. Blocking CXCR2 may be a promising therapeutic approach for ICC.