Ailanthone inhibits bladder cancer tumor and cell proliferation, epithelial-mesenchymal transition, and activation of the Janus kinase/signal transducer and activator of transcription 3 signaling pathway.

Abstract

Objective: Ailanthone (AIL), a medicinal component with antitumor properties, was distilled from Ailanthus altissima. The aim of this work was to probe the cancer-fighting effect of AIL on bladder cancer (BC) cells and the molecular basis of this effect.

Material and methods: We developed a subcutaneous BC mouse model and then administered AIL treatment. The effects of AIL on tumor tissue integrity and apoptosis were analyzed using hematoxylin and eosin (H&E) staining and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining methods. Furthermore, we investigated the effect of AIL on the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway and associated proteins through quantitative reverse transcription polymerase chain reaction and Western blot analysis. Various concentrations of AIL were applied to BC cells, and its effects on cell survival, motility, and apoptosis were detected through cell counting kit-8 assay, Transwell assay, and flow cytometry. In addition, we examined the influence of AIL on apoptosis-related proteins and epithelialmesenchymal transition (EMT)-related proteins in BC cells through Western blot analysis.

Results: AIL significantly suppressed the growth and migration of 5637 and T24 cells while promoting apoptosis (P < 0.05, P < 0.01, and P < 0.001). In addition, AIL increased the levels of cell death-associated proteins (P < 0.05, P < 0.01, and P < 0.001) and reversed EMT in BC cells. In vivo, AIL treatment reduced tumor growth and lowered the transcriptional levels of interleukin (IL)-6, IL-10, and IL-23, which are activation factors in the JAK/STAT3 signaling pathway. It also decreased the phosphorylation levels of JAK1, JAK2, and STAT3 in tumor tissues (P < 0.05 and P < 0.01).

Conclusion: AIL exhibits multiple anticancer effects, such as BC cell growth suppression, apoptosis enhancement, reversion of EMT reversion, tumor growth, and JAK/STAT3 pathway activation suppression.