Arsenic trioxide inhibits Skp2 expression to increase chemosensitivity to gemcitabine in pancreatic cancer cells.

The S-phase kinase associated protein 2 (Skp2), a member of the F-box protein family, regulates cell cycle progression and is highly expressed in pancreatic cancer (PC). Recently, we reported that arsenic trioxide (ATO) inhibited cell growth and invasion via downregulation of Skp2 in PC cells. Emerging evidence has revealed that Skp2 plays a crucial role in drug resistance in several kinds of cancers. Here, we determined whether ATO enhanced the sensitivity of PC cell lines to gemcitabine (GEM). We found that the combined treatment of ATO and GEM demonstrated strong antitumor effects in Patu8988 and Panc-1 PC cells. In addition, ATO potentiated the effects of GEM via downregulation of the Skp2 pathway in PC cells. Together, these findings suggested that Skp2 may be a promising therapeutic target to overcome resistance to GEM in PC.