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

• Main Authors: Wu LW, Zhang JK, Rao M, Zhang ZY, Zhu HJ, Zhang C
• Format: Article
• Language: English
• Published: Dove Medical Press 2019-06-01
• Series: OncoTargets and Therapy
• Subjects: Harmine; gemcitabine; pancreatic cancer; AKT/mTOR; combination
• Online Access: https://www.dovepress.com/harmine-suppresses-the-proliferation-of-pancreatic-cancer-cells-and-se-peer-reviewed-article-OTT

Lin-Wen Wu,1,2,* Jian-Kang Zhang,1,2,* Mingjun Rao,3 Zuo-Yan Zhang,1,2 Hua-Jian Zhu,1,2 Chong Zhang1,21School 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 workPurpose: 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