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Pharmacognosy MagazineNOW IN
Article

Phenolic alkaloids from Menispermum dauricum inhibits BxPC‑3 pancreatic cancer cells by blocking of Hedgehog signaling pathway

2★, 3★, 2,4, 5★, 6★ Corresponding author

  1. 1Research Institute of Traditional Chinese Medicine, China.
  2. 2The Fourth Affiliated Hospital, Harbin Medical University, China.
  3. 3Department of Qiqihar Medical University, Basic Medicine, Heilongjiang, China.
  4. 4Department of Pathology, The First Affiliated Hospital, China.
  5. 5Basic Medical College, Heilongjiang University of Chinese Medicine, China.

CORRESPONDENCE

Zhong-guang Zhou

The Fourth Affiliated Hospital, Harbin Medical University, China.

zhonglili2015@163.com

Received: 03-12-2014; Revised: 05-02-2015.

Volume 11, Issue 44 · pp. 690–697 · 2015 · DOI: 10.4103/0973-1296.165548

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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.

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    Zhou, Z., Zhang, C., Fei, H., Zhong, L., & Bai, Y. (2015). Phenolic alkaloids from Menispermum dauricum inhibits BxPC‑3 pancreatic cancer cells by blocking of Hedgehog signaling pathway. Pharmacognosy Magazine, 11(44), 690–697. https://doi.org/10.4103/0973-1296.165548