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.
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Article info
Publication history
Published online: January 06, 2014
Accepted:
December 31,
2013
Footnotes
Supported by Grant-in-aid for Scientific Research (No. 21591765) from Japan Society for the Promotion of Science and the Ministry of Health.
Identification
Copyright
© 2014 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
