title: Blockage of CXCR2 suppresses tumor growth of intrahepatic cholangiocellular carcinoma.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Sueoka
authors.affiliation: Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Tadamichi
authors.initials: T
authors.lastname: Hirano
authors.affiliation: Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Yugo
authors.initials: Y
authors.lastname: Uda
authors.affiliation: Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Iimuro
authors.affiliation: Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Yamanaka
authors.affiliation: Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan. Electronic address: sfujimo@hyo-med.ac.jp.
authors.forename: Jiro
authors.initials: J
authors.lastname: Fujimoto
mesh_terms: D000818:Animals; D001650:Bile Duct Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D001653:Bile Ducts, Intrahepatic; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D018281:Cholangiocarcinoma / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010671:Phenylurea Compounds / Q000494:pharmacology; D011379:Prognosis; D034741:RNA, Small Interfering / Q000494:pharmacology; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D016209:Interleukin-8; D010671:Phenylurea Compounds; D034741:RNA, Small Interfering; D023063:Receptors, Interleukin-8B; C112019:SB 225002