Synergistic reversal effect of epithelial-to-mesenchymal transition by miR-223 inhibitor and genistein in gemcitabine-resistant pancreatic cancer cells.

Emerging studies have demonstrated that EMT phenotype is closely related with tumor progression and drug resistance in a variety of human cancers. Recently, it has been extensively demonstrated that microRNAs (miRNAs) play a pivotal role in regulating EMT. In our previously reports, we have reported that inhibition of miR-223 could reverse EMT phenotype and improve chemotherapeutic drug sensitivity. We also reported that genistein down-regulated miR-223 expression in gemcitabine-resistant (GR) pancreatic cancer cells. Here, we explored whether there was the synergistic effect between miR-223 inhibitor and genistein on cell growth, migration, invasion and reversal of EMT in GR pancreatic cancer. We found that the combination of miR-223 inhibitor and genistein synergistically reduced cell motility and invasion and enhanced gemcitabine sensitivity in GR cells. In addition, we further observed that miR-223 inhibitor and genistein reversed EMT features in GR cells. This study suggests that the combination of miR-223 inhibitor and genistein may be a potential therapeutic strategy for the treatment of pancreatic cancer.