2011年10月
Overexpression of cIAP2 contributes to 5-FU resistance and a poor prognosis in oral squamous cell carcinoma
BRITISH JOURNAL OF CANCER
- 巻
- 105
- 号
- 9
- 開始ページ
- 1322
- 終了ページ
- 1330
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1038/bjc.2011.387
- 出版者・発行元
- NATURE PUBLISHING GROUP
BACKGROUND: Resistance to 5-fluorouracil (5-FU) is a major obstacle in treating oral squamous cell carcinoma (OSCC). However, little is known about apoptosis resistance, which contributes to 5-FU resistance in OSCC.
METHODS: We focussed on the cellular inhibitor of apoptosis protein 2 (cIAP2) on the basis of a DNA microarray data using parental and 5-FU-resistant OSCC cell lines. The effects of cIAP2 downregulation on 5-FU sensitivity and apoptosis were evaluated. An immunohistochemical analysis of cIAP2 and related proteins, cIAP1 and X-linked IAP, was performed in 54 OSCC patients who were treated with 5-FU-based chemoradiotherapy and surgery.
RESULTS: The downregulation of cIAP2 significantly enhanced the sensitivity of the 5-FU-resistant cells to 5-FU, with a significant increase in apoptosis. The immunohistochemical analysis demonstrated a high cIAP2 tumour expression to significantly correlate with the pathological response to chemoradiotherapy. Furthermore, a Cox regression analysis revealed the cIAP2 expression status (hazard ratio, 4.91; P = 0.037) and the pathological response to chemoradiotherapy (hazard ratio, 0.418; P = 0.016) to be significant prognostic factors for OSCC patients.
CONCLUSION: These novel findings demonstrate that cIAP2 may represent a potentially useful therapeutic target for improving the treatment and survival of OSCC patients, particularly in the setting of 5-FU resistance. British Journal of Cancer (2011) 105, 1322-1330. doi:10.1038/bjc.2011.387 www.bjcancer.com Published online 27 September 2011 (C) 2011 Cancer Research UK
METHODS: We focussed on the cellular inhibitor of apoptosis protein 2 (cIAP2) on the basis of a DNA microarray data using parental and 5-FU-resistant OSCC cell lines. The effects of cIAP2 downregulation on 5-FU sensitivity and apoptosis were evaluated. An immunohistochemical analysis of cIAP2 and related proteins, cIAP1 and X-linked IAP, was performed in 54 OSCC patients who were treated with 5-FU-based chemoradiotherapy and surgery.
RESULTS: The downregulation of cIAP2 significantly enhanced the sensitivity of the 5-FU-resistant cells to 5-FU, with a significant increase in apoptosis. The immunohistochemical analysis demonstrated a high cIAP2 tumour expression to significantly correlate with the pathological response to chemoradiotherapy. Furthermore, a Cox regression analysis revealed the cIAP2 expression status (hazard ratio, 4.91; P = 0.037) and the pathological response to chemoradiotherapy (hazard ratio, 0.418; P = 0.016) to be significant prognostic factors for OSCC patients.
CONCLUSION: These novel findings demonstrate that cIAP2 may represent a potentially useful therapeutic target for improving the treatment and survival of OSCC patients, particularly in the setting of 5-FU resistance. British Journal of Cancer (2011) 105, 1322-1330. doi:10.1038/bjc.2011.387 www.bjcancer.com Published online 27 September 2011 (C) 2011 Cancer Research UK
- リンク情報
- ID情報
-
- DOI : 10.1038/bjc.2011.387
- ISSN : 0007-0920
- PubMed ID : 21952624
- Web of Science ID : WOS:000296282000010