Luteolin suppresses the growth of colon cancer cells by inhibiting the IL-6/STAT3 signaling pathway

Jingwen Jiang; Fengting Zhu; Hui Zhang; Tao Sun; Fangfang Fu; Xuewu Chen; Yanhong Zhang

doi:10.21037/jgo-22-507

Luteolin suppresses the growth of colon cancer cells by inhibiting the IL-6/STAT3 signaling pathway

J Gastrointest Oncol. 2022 Aug;13(4):1722-1732. doi: 10.21037/jgo-22-507.

Authors

Jingwen Jiang¹, Fengting Zhu¹, Hui Zhang¹, Tao Sun², Fangfang Fu¹, Xuewu Chen¹, Yanhong Zhang³

Affiliations

¹ Department of Medical Oncology, Hainan Province Hospital of Traditional Chinese Medicine, Haikou, China.
² Hainan Medical University, Haikou, China.
³ Department of Traditional Chinese Medicine, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.

Abstract

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.

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.

Keywords: Interleukin 6 (IL-6); colon cancer; lipopolysaccharide (LPS); luteolin; signal transducer and activator of transcription 3 (STAT3).