title: Enhanced chemosensitization in multidrug-resistant human breast cancer cells by inhibition of IL-6 and IL-8 production.
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.
authors.affiliation: RayBiotech, Inc, Guangzhou, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Shi
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Yang
authors.forename: Li-Pai
authors.initials: LP
authors.lastname: Chen
authors.forename: Dong-Hua
authors.initials: DH
authors.lastname: Yang
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.forename: Jin
authors.initials: J
authors.lastname: Zhu
authors.forename: Jun-Jiang
authors.initials: JJ
authors.lastname: Chen
authors.forename: Ruo-Chun
authors.initials: RC
authors.lastname: Huang
authors.forename: Zhe-Sheng
authors.initials: ZS
authors.lastname: Chen
authors.forename: Ruo-Pan
authors.initials: RP
authors.lastname: Huang
mesh_terms: D057134:Antibodies, Neutralizing / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D001483:Base Sequence; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D061986:MCF-7 Cells; D008969:Molecular Sequence Data; D017239:Paclitaxel / Q000494:pharmacology; D034741:RNA, Small Interfering; D019947:Receptors, Interleukin-6 / Q000235:genetics; D053700:Receptors, Interleukin-8 / Q000235:genetics; D000093242:Interleukin-6 Inhibitors
chemical_list: D057134:Antibodies, Neutralizing; D000970:Antineoplastic Agents; D018932:Chemokine CCL2; D016207:Cytokines; D004317:Doxorubicin; D015850:Interleukin-6; D016209:Interleukin-8; D017239:Paclitaxel; D034741:RNA, Small Interfering; D019947:Receptors, Interleukin-6; D053700:Receptors, Interleukin-8; D000093242:Interleukin-6 Inhibitors; C111835:CCL2 protein, human