Interleukin 22 protects colorectal cancer cells from chemotherapy by activating the STAT3 pathway and inducing autocrine expression of interleukin 8.

Abstract

Resistance to chemotherapy is the major cause of colorectal cancer (CRC) treatment failure. The cytokine IL-22, which is produced by T cells and NK cells, is associated with tumorigenesis and tumor progression in cancers. However, the role of IL-22 in chemoresistance has not been investigated. We found that IL-22 levels in tumor tissues and peripheral blood were associated with chemoresistance and indicate poor prognosis for patients who received FOLFOX chemotherapy. In CRC cells, IL-22 was able to attenuate the cytotoxic and apoptosis-inducing effects of 5-FU and OXA by activating the STAT3 pathway and subsequently increasing the expression of anti-apoptotic genes. In addition, IL-22 conferred resistance to 5-FU and OXA by inducing IL-8 autocrine expression through STAT3 activation. Our findings identify IL-22 as a novel chemoresistance cytokine and may be a useful prognostic biomarker for CRC patients receiving FOLFOX chemotherapy.

• Authors: Tingyu Wu, Zhongchuan Wang, Yun Liu, Zubing Mei, Guanghui Wang, Zhonglin Liang, Ang Cui, Xuguang Hu, Long Cui, Yili Yang, Chen-Ying Liu
• Journal: Clinical immunology (Orlando, Fla.) (Clin Immunol) Vol. 154 Issue 2 Pg. 116-26 (Oct 2014) ISSN: 1521-7035 [Electronic] United States
• PMID: 25063444 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Interleukin-8
• Interleukins
• Organoplatinum Compounds
• STAT3 Transcription Factor
• STAT3 protein, human
• Leucovorin
• Fluorouracil
• interleukin-22

Topics

• Antineoplastic Agents (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Autocrine Communication
• Cell Line, Tumor
• Colorectal Neoplasms (drug therapy)
• Drug Resistance, Neoplasm
• Fluorouracil (therapeutic use)
• Gene Expression Regulation, Neoplastic (physiology)
• Humans
• Interleukin-8 (genetics, metabolism)
• Interleukins (genetics, metabolism)
• Leucovorin (therapeutic use)
• Organoplatinum Compounds (therapeutic use)
• STAT3 Transcription Factor (genetics, metabolism)
• Treatment Failure