Overexpression of CXCR4 is significantly associated with cisplatin-based chemotherapy resistance and can be a prognostic factor in epithelial ovarian cancer
2
조회
0
다운로드
4
인용
0
참고문헌
키워드
초록
The chemokine receptor 4 (CXCR4) plays an important role inthe growth, angiogenesis and metastasis of various cancers,including epithelial ovarian cancer (EOC). However, thecorrelation between CXCR4 and the clinical response of EOCpatients to chemotherapy remains unknown. 124 EOC patientswere recruited to assess the relationship between CXCR4 andthe response to cisplatin-based chemotherapy. The resultsshowed that patients with a higher CXCR4 expression had asignificantly lower chemosensitivity, a poorer progression-freesurvival and a lower overall survival than those with lowerCXCR4 expression. In addition, knockdown of CXCR4 by smallinterfering RNA suppressed cell proliferation and resulted inG1/S arrest, increased apoptosis and chemosensitivity in bothcisplatin-sensitive A2780 cells and cisplatin-resistant cellA2780/cis in vitro. Our data suggest that CXCR4 is one of thekey molecules in cisplatin-based chemotherapy for EOCpatients and that CXCR4 inhibition is a potential strategy toaddress the chemoresistance of EOC.
Abstract
The chemokine receptor 4 (CXCR4) plays an important role inthe growth, angiogenesis and metastasis of various cancers,including epithelial ovarian cancer (EOC). However, thecorrelation between CXCR4 and the clinical response of EOCpatients to chemotherapy remains unknown. 124 EOC patientswere recruited to assess the relationship between CXCR4 andthe response to cisplatin-based chemotherapy. The resultsshowed that patients with a higher CXCR4 expression had asignificantly lower chemosensitivity, a poorer progression-freesurvival and a lower overall survival than those with lowerCXCR4 expression. In addition, knockdown of CXCR4 by smallinterfering RNA suppressed cell proliferation and resulted inG1/S arrest, increased apoptosis and chemosensitivity in bothcisplatin-sensitive A2780 cells and cisplatin-resistant cellA2780/cis in vitro. Our data suggest that CXCR4 is one of thekey molecules in cisplatin-based chemotherapy for EOCpatients and that CXCR4 inhibition is a potential strategy toaddress the chemoresistance of EOC.
참고문헌 (21)
- Siegel, R., "Cancer statistics, 2012", CA, 62, pp.10~29 (2012)
- Sudo, T., "Molecular-targeted therapies for ovarian cancer: prospects for the future", Int. J. Clin. Oncol, 17, pp.424~429 (2012)
- Sueblinvong, T., "Establishment, characterization and downstream application of primary ovarian cancer cells derived from solid tumors", PLOS One, 7, pp.e50519~ (2012)
- Teicher, B. A., "CXCL12 (SDF-1)", CXCR4 pathway in cancer, 2010, pp.16, 2927~2931
- Ying, J., "The expression of CXCL12 and CXCR4 in gastric cancer and their correlation to lymph node metastasis", Med. Oncol, 29, pp.1716~1722 (2012)
- Yang, S. X., "Decreased expression of C-erbB-2 and CXCR4 in breast cancer after primary chemotherapy", J. Transl. Med, 10(Suppl 1), pp.S3~ (2012)
- Murakami, T., "The role of CXCR3 and CXCR4 in colorectal cancer metastasis", Int. J. Cancer, 132, pp.276~287 (2013)
- Jung, M. J., "Upregulation of CXCR4 is functionally crucial for maintenance of stemness in drug-resistant non-small cell lung cancer cells", Oncogene, 32, pp.209~221 (2013)
- Sekiya, R., "Expression of CXCR4 indicates poor prognosis in patients with clear cell carcinoma of the ovary", Hum. Pathol, 43, pp.904~910 (2012)
- Domanska, U. M., "CXCR4 inhibition with AMD3100 sensitizes prostate cancer to docetaxel chemotherapy", Neoplasia, 14, pp.709~718 (2012)
- Yu, T., "RNAi targeting CXCR4 inhibits tumor growth through inducing cell cycle arrest and apoptosis", Mol. Ther, 20, pp.398~407 (2012)
- Chen, G., "Inhibition of chemokine (CXC motif) ligand 12", chemokine (CXC motif) receptor 4 axis (CXCL12, J. Biol. Chem, pp.2012, 287[DOI]
- Dubrovska, A., "CXCR4 expression in prostate cancer progenitor cells", PLOS One, 7, pp.e31226~ (2012)
- Dubrovska, A., "CXCR4 activation maintains a stem cell population in tamoxifen- resistant breast cancer cells through AhR signalling", Brit. J. Cancer, 107, pp.43~52 (2012)
- Wang, J., "Silencing of CXCR4 blocks progression of ovarian cancer and depresses canonical Wnt signaling pathway", Int. J. Gynecol. Cancer, 21, pp.981~987 (2011)
- Kim, J., "Identification of anti-malarial compounds as novel antagonists to chemokine receptor CXCR4 in pancreatic cancer cells", PLOS One, 7, pp.e31004~ (2012)
- Guo, P., "Using breast cancer cell CXCR4 surface expression to predict liposome binding and cytotoxicity", Biomaterials, 33, pp.8104~8110 (2012)
- Zhou, Z., "Establishment of a biomarker model for predicting bone metastasis in resected stage III non-small cell lung cancer", J. Exp. Clin. Canc. Res, 31, pp.34~ (2012)
- Wang, L., "Silencing of CXCR4 by RNA interference inhibits cell growth and metastasis in human renal cancer cells", Oncol. Rep, 28, pp.2043~2048 (2012)
- Scala, S., "Expression of CXCR4 predicts poor prognosis in patients with malignant melanoma", Clin. Cancer Res, 11, pp.1835~1841 (2005)
- Kim, M., "CXCR4 signaling regulates metastasis of chemoresistant melanoma cells by a lymphatic metastatic niche", Cancer Res, 70, pp.10411~10421 (2010)