Journal
BREAST CANCER RESEARCH AND TREATMENT
Volume 135, Issue 3, Pages 737-747Publisher
SPRINGER
DOI: 10.1007/s10549-012-2196-0
Keywords
Cytokine; IL-6; IL-8; Drug resistance; Cytokine antibody arrays
Categories
Funding
- leading scientist project for Guangzhou economic development district [2009L-P180]
- Guangzhou leading talent entrepreneurial venture [LCY201111]
- Guangdong innovative research and development team [201001s0104659419]
- Guangzhou economic development district [2010Q-P450]
- National Institute of Health [1R15CA143701]
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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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