Background
Despite the remarkable progression in colon cancer treatment in recent years, the pathological mechanism underlying this disease remains unclear. This study aimed to discuss the potential of luteolin in the treatment of colon cancer, from the perspective of traditional Chinese medicine, with a particular focus on the tumor microenvironment.
Conclusions
Luteolin suppressed the growth and migration/invasion potential of colon cancer cells by inhibiting the IL-6/STAT3 signaling pathway.
Methods
Reverse transcription quantitative polymerase chain reaction and western blot were used to analyze the effects of luteolin on interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3)/Phospho-STAT3. Enzyme-linked immunosorbent assay was used to analyze the protein secretion of IL-6. Proliferation and transwell assays were used to analyze the growth and migration of luteolin and IL-6 in colon cancer cells, respectively.
Results
Stimulation with lipopolysaccharides (LPS) promoted the M1 polarization of macrophages and increased the expression and secretion of IL-6. However, the presence of luteolin inhibited the effects of LPS. M1 polarization increased the proliferation rate, migration and invasion ability, and phosphorylation of STAT3 in colon cancer cells (SW620 and SW480). Luteolin inhibited these effects by reducing M1 polarization. To confirm that the action of luteolin is mediated by IL-6/STAT3 signaling, we treated SW620 and SW480 cells with recombinant IL-6 protein and anti-IL-6 antibody. IL-6 was observed to promote cell proliferation, enhance migration and invasion, and increase STAT3 phosphorylation. The opposite effect was observed with the anti-IL-6 antibody. In addition, IL-6 promoted LPS-induced M1 polarization, while the anti-IL-6 antibody enhanced the decrease in luteolin-induced M1 polarization. Conclusions: Luteolin suppressed the growth and migration/invasion potential of colon cancer cells by inhibiting the IL-6/STAT3 signaling pathway.