Harmine suppresses the proliferation of pancreatic cancer cells and sensitizes pancreatic cancer to gemcitabine treatment
| Autor: | Zuo-Yan Zhang, Jiankang Zhang, Ming‐jun Rao, Chong Zhang, Hua-Jian Zhu, Lin-wen Wu |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
business.industry Cancer Cell cycle medicine.disease Gemcitabine 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Harmine Oncology chemistry Apoptosis 030220 oncology & carcinogenesis Pancreatic cancer medicine Cancer research Pharmacology (medical) business Protein kinase B PI3K/AKT/mTOR pathway medicine.drug |
| Zdroj: | OncoTargets and Therapy. 12:4585-4593 |
| ISSN: | 1178-6930 |
| DOI: | 10.2147/ott.s205097 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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