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.Materials and 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.Conclusion: 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.

Keywords: BxPC‑3; Gli‑1; pancreatic cancer; phenolic alkaloids from Menispermum dauricum; Sonic Hedgehog