Involvement of TNF-alpha and IL-10 in breast cancer and patient survival

Abstract

Purpose: To investigate the involvement of tumor necrosis factor α (TNF-α) and interleukin 10 (IL-10) in the pathogenesis of breast cancer in vivo as well as the activity of ten Chinese herbal compounds in human breast cancer (MCF-7) cell proliferation in vitro. Methods: In the in vivo study, the association of serum TNF-α and IL-10 with breast cancer cell invasiveness and prognosis was determined in female patients (n = 192) with breast cancer, while in the in vitro study, ten herbal Chinese compounds were screened for their effectiveness against MCF-7 cells. The levels of TNF-α, IL-10, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2/neu) were assayed using their respective enzyme-linked immunosorbent assay (ELISA) kits. Molecular docking was used to determine the lead compound(s) that can effectively inhibit TNF-α and IL-10. Results: Raised serum levels of TNF-α and IL-10 were significantly associated with breast cancer cell invasiveness and poor prognosis (p < 0.05). Moreover, there was a strong association between breast cancer prognosis and the expression levels of ER, PR and HER2/neu. Serum TNF-α and IL-10 levels were significantly elevated in stages II and III patients and in those with lymph node metastasis. Treatment of MCF-7 cells with the herbal compounds significantly reduced the synthesis and release of TNF-α and IL-10 (p < 0.05). The results of molecular docking showed that baicalein and oridonin significantly inhibited TNF- α and IL-10. The two herbal compounds had the highest docking scores for inhibition of cytokines, as well as favorable interaction energies. Conclusion: These results indicate that TNF-α and IL-10 are involved in the pathogenesis of breast cancer, and that baicalein and oridonin effectively inhibit the proliferation of the cells.