Dauricine suppresses the growth of pancreatic cancer in vivo by modulating the Hedgehog signaling pathway

Abstract

Pancreatic cancer is a highly malignant cancer associated with high expression levels of sonic hedgehog signaling molecule (Shh), patched 1 (Ptch1), smoothened frizzled class receptor (Smo) and glioma-associated oncogene family zinc finger 1 (Gli1) in the hedgehog (Hh) signaling pathway. Inhibition of the Hh signaling pathway is a potential therapeutic target for pancreatic cancer. The aim of the present study was to investigate the effects of dauricine in a pancreatic cancer BxPC-3 xenograft animal model and examine the underlying molecular mechanisms through Hh signaling pathway. High-and low-dose dauricine treatment significantly suppressed tumor growth with no concomitant effect on the spleen index. In addition, dauricine induced apoptosis and cell cycle arrest in pancreatic cancer BxPC-3 cells. The inhibitory effects of dauricine on pancreatic cancer may be mediated by the suppression of the Hh signaling pathway, as indicated by the decreases in the gene and protein expression levels of Shh, Ptch1, Smo and Gli1. The effects of dauricine were similar to those of 5-fluorouracil. Dauricine, a naturally occurring alkaloid, may be a potential anticancer agent for the treatment of pancreatic cancer.