Silencing Interleukin-6 and Glycoprotein 130 Suppresses Growth and Induces Apoptosis in Cancer Cells

Abstract

Background: Various signaling pathways promote cancer growth and inhibit apoptosis in cancerous cells. The increased levels of interleukin (IL)-6 cytokine and its signaling by IL-6 receptors have been reported in various cancers, which were associated with poor prognosis. On the other hand, targeting IL-6 and IL-6 receptors was associated with ameliorating effects in cancers. Therefore, this study sought to inhibit both IL-6 and its receptor (glycoprotein 130, [gp130]) and to synergistically reduce cancer progression in vitro. Methods: Accordingly, 4T1 and CT26 cancer cell lines were used to analyze the efficacy of the simultaneous blockade of IL-6 and gp130. In addition, small interfering ribonucleic acid (siRNA) molecules were employed to suppress the expression of these factors. The expression of target genes was investigated using the quantitative real-time polymerase chain reaction assay. Further, an MTT assay was applied to study cell survival. Finally, cytokine was measured by enzyme-linked immunosorbent assay. Results: The transfection of cancer cells by lipofectamine led to significant downregulation of these factors in both cell lines. Moreover, the downregulation of IL-6 and gp130 caused significant cell death induction, which was associated with the reduced proliferative potential of both cells. Eventually, IL-6 silencing markedly suppressed the secretion of IL-6 in both cells. Conclusion: These findings imply that the simultaneous silencing of IL-6 and gp130 can be considered a potential anticancer therapeutic approach that should be further considered in future studies.