title: Phenolic alkaloids from Menispermum dauricum inhibits BxPC-3 pancreatic cancer cells by blocking of Hedgehog signaling pathway.
abstract: BACKGROUND
  The Hedgehog (Hh) signaling pathway plays an important role in pancreatic cancer (PC) cells. Phenolic alkaloids from Menispermum dauricum (PAMD), a traditional Chinese medicine used for the treatment of immune disorders, have been reported to have antitumor activity recently.
  
  
  OBJECTIVE
  To investigate the efficacy and mechanism of PAMD against PC cell BxPC-3.
  
  
  METHODS
  F assay was used to assess cell proliferation inhibition of PAMD; the apoptotic induction and cell cycle arrest was detected by flow cytometry; the BxPC-3 xenograft was established to evaluate the tumor growth inhibition of PAMD; hematoxylin-eosin staining was applied to analyze the pathological morphology of tumor tissues; immunohistochemistry (IHC) and Western blot was adopted to detect the protein levels; quantitative real-time polymerase chain reaction was used to determine the mRNA expressions.
  
  
  RESULTS
  PAMD shows time-and dose-dependent proliferation inhibition on the BxPC-3 cell, induced G0/G1 phase arrest and cell apoptosis in vitro. PAMD also showed better inhibition of tumor growth and a preferable safety profile compared with chemotherapeutic regimen 5-fluoro-2, 4 (1 H, 3 H) pyrimidinedione in BxPC-3 xenograft in vivo. Furthermore, PAMD directly decreases the protein and mRNA levels of Sonic Hedgehog (Shh) and its downstream transcription factor Gli-1 in the BxPC-3 tumor tissues.
  
  
  CONCLUSIONS
  The treatment of PAMD displayed Hh signaling pathway blockade through decreasing the protein and mRNA levels of Shh and its downstream transcription factor Gli-1, suggesting a promising strategy in treating human PC.
authors.affiliation: Research Institute of Traditional Chinese Medicine, Heilongjiang, China.
authors.forename: Zhong-Guang
authors.initials: ZG
authors.lastname: Zhou
authors.affiliation: The Fourth Affiliated Hospital, Harbin Medical University, Heilongjiang, China.
authors.forename: Chao-Ying
authors.initials: CY
authors.lastname: Zhang
authors.affiliation: Research Institute of Traditional Chinese Medicine, Heilongjiang, China ; Department of Qiqihar Medical University, Basic Medicine, Heilongjiang, China.
authors.forename: Hong-Xin
authors.initials: HX
authors.lastname: Fei
authors.affiliation: Department of Pathology, The First Affiliated Hospital, Heilongjiang, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Zhong
authors.affiliation: Basic Medical College, Heilongjiang University of Chinese Medicine, Heilongjiang, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Bai
keywords: BxPC-3; Gli-1; Sonic Hedgehog; pancreatic cancer; phenolic alkaloids from Menispermum dauricum