Alkaloids from Evodia rutaecarpa inhibit the occurrence and development of gallbladder cancer in vivo and in vitro.

UNLABELLED: Objective Gallbladder cancer (GBC) poses a significant health burden with dismal prognosis due to frequent metastasis and recurrence. Although evodiamine has demonstrated potent inhibitory effects on proliferation and metastasis in various cancers, its role in GBC remains unexplored, and the underlying mechanisms are yet to be elucidated.

METHODS

The inhibitory effects of evodiamine on GBC cells were evaluated in vitro using a cell viability assay. Cell migration capacity was assessed via wound healing and Transwell assays. Apoptosis and cell cycle distribution were analyzed by flow cytometry and Western blotting (WB). The molecular mechanisms were investigated using Quantitative polymerase chain reaction (qPCR) and WB to quantify ZEB1 gene expression. In vivo, the anti-tumor activity of evodiamine was verified in a nude mouse model.

RESULTS

Evodiamine significantly inhibited the proliferation of GBC cells. Flow cytometry and Western blotting revealed that evodiamine induced G2/M phase arrest and promoted apoptosis. mRNA-sequencing (mRNA-seq) demonstrated that evodiamine suppressed the transcription of ZEB1 and genes in the PI3K-Akt signaling pathway. Consistent with in vitro findings, evodiamine exhibited remarkable antitumor effects in a nude mouse model.

CONCLUSION

This study confirms that evodiamine inhibits GBC cell proliferation and induces apoptosis. The mechanism involves suppression of ZEB1 expression and inactivation of the PI3K-Akt signaling pathway.