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01-10-2012 | Preclinical Study

Enhanced chemosensitization in multidrug-resistant human breast cancer cells by inhibition of IL-6 and IL-8 production

Authors: Zhi Shi, Wei-Min Yang, Li-Pai Chen, Dong-Hua Yang, Qi Zhou, Jin Zhu, Jun-Jiang Chen, Ruo-Chun Huang, Zhe-Sheng Chen, Ruo-Pan Huang

Published in: Breast Cancer Research and Treatment | Issue 3/2012

Abstract

Drug resistance remains a major hurdle to successful cancer treatment. Many mechanisms such as overexpression of multidrug-resistance related proteins, increased drug metabolism, decreased apoptosis, and impairment of signal transduction pathway can contribute multidrug resistance (MDR). Recent studies strongly suggest a close link between cytokines and drug resistance. To identify new targets involved in drug resistance, we established a multidrug-resistant human breast cancer cell line MCF-7/R and examined the cytokine profile using cytokine antibody array technology. Among 120 cytokines/chemokines screened, IL-6, IL-8, and 13 other proteins were found to be markedly increased in drug-resistant MCF-7/R cell line as compared to sensitive MCF-7/S cell line, while 7 proteins were specifically reduced in drug-resistant MCF-7/R cells. Neutralizing antibodies against IL-6 and IL-8 partially reversed the drug resistance of MCF-7/R to paclitaxel and doxorubicin, while a neutralizing antibody against MCP-1 had no significant effect. Inhibition of endogenous IL-6 or IL-8 by siRNA technology significantly enhanced drug sensitivity of MCF-7/R cells. Furthermore, overexpression of IL-6 or IL-8 expression by transfection increased the ADM resistance in MCF-7/S cells. Our data suggest that increased expression levels of IL-6 and IL-8 may contribute to MDR in human breast cancer cells.

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Title: Enhanced chemosensitization in multidrug-resistant human breast cancer cells by inhibition of IL-6 and IL-8 production
Authors: Zhi Shi
Wei-Min Yang
Li-Pai Chen
Dong-Hua Yang
Qi Zhou
Jin Zhu
Jun-Jiang Chen
Ruo-Chun Huang
Zhe-Sheng Chen
Ruo-Pan Huang
Publication date: 01-10-2012
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 3/2012
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-012-2196-0

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