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Harmine suppresses the proliferation of pancreatic cancer cells and sensitizes pancreatic cancer to gemcitabine treatment

Authors Wu LW, Zhang JK, Rao M, Zhang ZY, Zhu HJ, Zhang C

Received 12 February 2019

Accepted for publication 21 May 2019

Published 12 June 2019 Volume 2019:12 Pages 4585—4593

DOI https://doi.org/10.2147/OTT.S205097

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Ms Aruna Narula

Peer reviewer comments 3

Editor who approved publication: Dr Yao Dai


Lin-Wen Wu,1,2,* Jian-Kang Zhang,1,2,* Mingjun Rao,3 Zuo-Yan Zhang,1,2 Hua-Jian Zhu,1,2 Chong Zhang1,2

1School of Medicine, Zhejiang University City College, Hangzhou, Zhejiang 310015, People’s Republic of China; 2College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China; 3Department of Clinical Pharmacology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, People’s Republic of China

*These authors contributed equally to this work

Purpose: Pancreatic carcinoma is one of the most deadliest types of cancer, and relatively insensitive to the currently available chemotherapy. Thus, the discovery of novel therapeutic agents to prolong the survival times of patients with pancreatic cancer is urgently required.
Methods: Cell proliferation was assessed using the sulforhodamine B and cell clone formation assay, apoptosis was analyzed through Annexin V/PI staining, analysis of cell cycle distribution was determined by PI staining, and the expression of proteins was detected via Western blotting.
Results: Our data showed that harmine exerted an anti-proliferative effect and cell cycle arrest at G2/M in pancreatic cancer cells. Meanwhile, harmine plus gemcitabine showed strong synergy in inhibiting the proliferation of pancreatic cancer cells. Furthermore, harmine induced apoptosis and enhanced the gemcitabine-induced apoptosis in pancreatic cancer cells. The AKT/mTOR pathway is involved in mechanisms of gemcitabine resistance in pancreatic cancer cells, our data demonstrated that harmine plus gemcitabine significantly suppressed the AKT/mTOR signaling pathway.
Conclusion: Harmine may be a potential candidate for the treatment of pancreatic cancer. Morever, the combination of harmine with gemcitabine appears to be an attractive option for the treatment of patients with pancreatic cancer.

Keywords: harmine, gemcitabine, pancreatic cancer, AKT/mTOR, combination

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