Paeonol Suppresses Proliferation and Motility of Non-Small-Cell Lung Cancer Cells by Disrupting STAT3/NF-κB Signaling

Abstract

Background: Targeting inflammatory microenvironment is a promising anti-tumor strategy. Paeonol is a phenolic compound with effective anti-inflammatory and anti-tumor properties. However, the effects of paeonol on non-small cell carcinoma (NSCLC) have not been fully investigated. Here, we evaluated the effects of paeonol on proliferation and metastasis of NSCLC and elucidated the underlying mechanisms.Methods: The effects of paeonol on inflammatory cytokines were determined by cell proliferation and ELISA assays. Assays of wound healing, single cell migration and perforation invasion were used to evaluate migration and invasion of NSCLC cells. Expression of marker proteins in epithelial-mesenchymal transition (EMT) and matrix metalloproteinase (MMP) family enzymes were detected by Western blot assays. Nude mouse A549 cells transplantation tumor model was used to study the anti-lung cancer effects of paeonol in vivo. TUNEL stanining were used to detect the apoptosis of tumor cells in A549 lung cancer mice, and Ki67 analysis was used to detect the proliferation of tumor cells in A549 lung cancer mice. Immunohistochemistry was used to detect the effects of paeonol on signaling molecules in tumor tissues.Results: Paeonol inhibited A549 cancer cell migration and invasion in vitro. Paeonol inhibited secreaion of inflammatory cytokines in A549 cells, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and transforming growth factor (TGF)-β. Paeonol altered the expression of marker proteins involved in EMT and MMP family enzymes. In addition, paeonol inhibited the transcriptional activity of nuclear factor-κB (NF-κB) and phosphorylation of signal transducers and activators of transcription 3 (STAT3). Paeonol inhibited the growth of A549 cells transplanted tumors in nude mice.Conclusion: Paeonol potently inhibited NSCLC cell growth, migration and invasion associated with disruption of STAT3 and NF-κB pathways, suggesting that it could be a promising anti-metastatic candidate for tumor chemotherapy.

Sterculic Acid Alters Adhesion Molecules Expression and Extracellular Matrix Compounds to Regulate Migration of Lung Cancer Cells

“…We could not detect IL-6 expression in H1299 cells in concordance with Bihl and co-workers [81]. Molecules with NF-Kβ inhibitory activity reduce IL-6 expression in a STAT3 dependent manner in A549 cells, and they also reduce cell migration, invasion and alter EMT markers [82][83][84]. Furthermore, TLR4 knockdown reduces IL-6 levels and cell migration of A549 cell by Pi3K/AKT pathway inhibition [85].…”

Paeonol Inhibits the Development of Rheumatoid Arthritis Through the Formyl Peptide Receptor 2

“…In future studies, optimizing the structure of paeonol to nd more anti-in ammatory drugs is of signi cance for the development of subsequent target drugs In arthritis research, the most important thing is to look at the in ammatory effect of drugs on synovial cells. Consistent with previous research, Paeonol inhibited IL-6, IL-1β and TNF-α production and mRNA expression [22]. WRW4 blocked the inhibition of in ammatory cytokines in FLS cells induced by paeonol.…”

Astragalin Inhibits the Proliferation and Migration of Human Colon Cancer HCT116 Cells by Regulating the NF-κB Signaling Pathway

“…TNF-α is a major factor involved in inflammation-associated cancer and plays an important role in the spread and invasion of tumor cells. Cancer cell activation also can be induced by numerous agents, including TNF-α ( Zhang L. et al, 2020 ). This study evaluated the inhibitory effect of astragalin on TNF-α-induced in colon cancer HCT116 cells activated.…”

“…The nuclear factor-κB (NF-κB) signaling pathway as a key player was involved inflammation-induced tumor metastasis ( Zhang L. et al, 2020 ). The inflammatory response regulated by pro-inflammatory NF-κB transcription factors plays a crucial part in the development of colorectal cancer.…”