Work

Withaferin-A Inhibits Colorectal Cancer Growth and Metastasis By Targeting the HSP90/HIF-1α/EMT axis

Year: 2025

Type: article

Abstract: Introduction Withaferin-A (WA) derived from natural products can inhibit the growth and metastasis of colorectal cancer (CRC) in vitro and in vivo. Material and methods Transcriptome sequencing showed that the WA inhibited the epithelial-mesenchymal transition pathway (EMT), HSP90, and HIF-1α genes of CRC, and further experiments showed that WA inhibited HSP90, HIF-1α, E-Cadherin, and Co-IP, signifying that WA inhibits the protein interaction between HSP90 and HIF-1α. Knockdown of HIF-1α can reduce the migration and invasion capabilities of HCT116 and SW480 cells, and in vivo experiments have proved that HIF-1α knockdown SW480 lung metastasis cells have significantly reduced in numbers compared to the control group. Results The classic HSP90 inhibitor, 17-AAG, can inhibit the migration and invasion of HCT116 and SW480 cells. We performed Q-PCR and western blot and found that 17-AAG can inhibit HSP90 and HIF-1α of CRC. The overexpression of HSP90 on HIF-1α knockdown SW480 cells can reinstate the migration and invasion ability, HIF-1α protein expression level, and protein binding ability of HSP90 and HIF-1α in SW480 cells. Conclusions These findings indicate that WA inhibits CRC's growth, migration, and invasion by inhibiting the HSP90/HIF-1α/EMT axis. Our result showed that WA may be one of the potential targets for the management and eventual cure of CRC.

Source: Archives of Medical Science

DOI: 10.5114/aoms/196381