LAUSR

ABSTRACT The epithelial‐mesenchymal transition (EMT) plays a critical role in cancer progression, metastasis and drug resistance. The transcription factor(TF) and microRNA (miR) chimeric [SNAIL/miR‐34]:[ZEB/miR‐200] unit is the core regulatory system for the EMT process. Here, we proposed to assess the anti‐EMT abilities and explore the inherent pharmacological mechanisms of the classic hypoglycaemic agent metformin for colorectal cancer(CRC). For the EMT model, the TGF‐&bgr;‐induced CRC cell lines SW480 and HCT116 were treated with metformin. The viability, migration and invasion abilities of the cells were evaluated with the Cell Counting Kit‐8, wound‐healing and trans‐well assay. The alterations of the [SNAIL/miR‐34]:[ZEB/miR‐200] system and the EMT markers E‐cadherin and vimentin were detected by western blot, qPCR and immunofluorescent staining. Metformin exhibited inhibitory effects on the proliferation, migration and invasion of the CRC SW480 cells. The up‐regulation of E‐cadherin and the down‐regulation of vimentin for both SW480 and HCT116 cells revealed the anti‐EMT abilities of metformin. For the [SNAIL/miR‐34]:[ZEB/miR‐200] system, metformin increased miR‐200a, miR‐200c and miR‐429 levels and decreased miR‐34a, SNAIL1 and ZEB1 levels in the TGF‐&bgr;‐induced EMT. From immunofluorescence, we observed increased E‐cadherin and ZEB1 co‐expression in metformin‐treated cells. Metformin may perform bidirectional regulations of the [SNAIL/miR‐34]:[ZEB/miR‐200] system in the EMT process for colorectal cancer. Such regulation is expressed as the inhibition of EMT in general as well as an increased higher proportion of E/M hybrid cells in the total population.