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Shi Z , Yang WM , Chen LP , Yang DH , Zhou Q , Zhu J , Chen JJ , Huang RC , Chen ZS , Huang RP
Enhanced chemosensitization in multidrug-resistant human breast cancer cells by inhibition of IL-6 and IL-8 production
Breast Cancer Research and Treatment. 2012 Oct;135(3) :737-747
AbstractDrug 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.
NotesShi, Zhi Yang, Wei-Min Chen, Li-Pai Yang, Dong-Hua Zhou, Qi Zhu, Jin Chen, Jun-Jiang Huang, Ruo-Chun Chen, Zhe-Sheng Huang, Ruo-Pan 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] We would like to express our thanks for the support of the leading scientist project for Guangzhou economic development district (2009L-P180), Guangzhou leading talent entrepreneurial venture (LCY201111), Guangdong innovative research and development team (201001s0104659419), research grants from the Guangzhou economic development district (2010Q-P450) and partially support from National Institute of Health (No. 1R15CA143701). We also greatly appreciate Dr. Valerie Jones's comments on the manuscript. 39 Springer New york 003zb