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.

Anticancer and Anti-Inflammatory Properties of Ganoderma lucidum Extract Effects on Melanoma and Triple-Negative Breast Cancer Treatment

“…More specifically, a pretreatment with LPS determined an increased secretion of measured cytokines and metalloproteases. This response may be due to the presence of the TLR4 receptor on the membrane of the melanoma and breast cancer cells, as was demonstrated [12,13]. Pretreatment with extract significantly decreased the levels of IL-8, IL-6, MMP-2 and MMP-9 in the breast cancer cells (Figure 3A).…”

“…Similarly, interleukin-8 (IL-8), a chemokine with a defining CXC amino acid motif, is characterized by important tumorigenic and pro-angiogenic properties in both cancers and it is associated with poor prognosis [22,23]. Moreover, IL-8 over-expression is involved in the proliferation, metastasis, angiogenesis and sensitivity to chemotherapeutics in breast cancer, primarily through the activation of AKT and MAPK signaling which results in the increased activation of NF-κB [12,13]. Melanoma and breast cancer cells are able to release several interleukins such as IL-8 and IL-6 under pro-inflammatory conditions [24,25].…”

Taxotere-induced elevated expression of IL8 in carcinoma-associated fibroblasts of breast invasive ductal cancer

“…It was reported that IL8 may participate in modulating tumor cell susceptibility and aggressiveness in breast cancer (9,19). Furthermore, it was observed that elevated expression of IL8 by transfection increased the resistance to Adriamycin ® in breast cancer cells (20). The aforementioned studies provided rationale for the current study to investigate the effect of IL8 on chemotherapy response in breast cancer.…”

Progression of Luminal Breast Tumors Is Promoted by Ménage à Trois between the Inflammatory Cytokine TNFαand the Hormonal and Growth-Supporting Arms of the Tumor Microenvironment

“…As a result of TNF α + Estrogen + EGF stimulation, new cell subtypes have dominated the tumor cell population, expressing high levels of VLA6 and of the metastasis-related adhesion molecules CD44 and β 1, accompanied by high levels of CXCL8, CCL2, and MMPs that were released by the cells. Based on published findings [84–87], the elevation in β 1, CD44, and CXCL8 may very much stand in the basis of the high resistance to doxorubicin gained by the TNF α + Estrogen + EGF-stimulated cells.…”