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| 標題: | In Vitro and In Vivo Antitumor Effects of Pyrimethamine on Non-small Cell Lung Cancers |
| 作者: | Lin, Meng-Xian
Lin, Sheng-Hao
Lin, Chi-Chen
Yang, Ching-Chieh
Yuan, Sheau-Yun |
| 貢獻者: | Natl Chung Hsing Univ, Inst Biomed Sci
Changhua Christian Hosp, Dept Internal Med, Div Chest Med
Chi Mei Med Ctr, Dept Radiat Oncol
Natl Sun Yat Sen Univ, Inst Biomed Sci
Chia Nan Univ Pharm & Sci, Dept Pharm
Taichung Vet Gen Hosp, Dept Med Res
Hungkuang Univ, Dept Nursing |
| 關鍵字: | Non-small cell lung cancer (NSCLC)
pyrimethamine
cell cycle
apoptosis
mitochondrial damage |
| 日期: | 2018-06 |
| 上傳時間: | 2019-11-15 15:45:44 (UTC+8) |
| 出版者: | INT INST ANTICANCER RESEARCH |
| 摘要: | Background/Aim: Pyrimethamine (PYR), an antimalarial drug is known to inhibit various types of human cancer cells. The aim of this study was to investigate the anti-tumour effects of pyrimethamine (PYR) and its underlying molecular mechanisms using the human NSCLC cell line A549. Materials and Methods: PYR was dissolved in dimethyl sulfoxide to determine its apoptotic activity on A549 cells. Cell viability was determined by the MTT assay. Cell cycle, mitochondrial membrane potential, and Annexin V-FITC early apoptosis detection were evaluated by flow cytometry. Cyclin-dependent kinase (CDK) and Bcl-2 family protein expression was determined by western blotting. Results: PYR reduced cell viability percentage and induced G(0)/G(1) arrest, which was associated with down-regulation of cyclins D1 and E, CDK4, and CDK2, and up-regulation of p21. PYR induced sub-G(1) accumulation, Annexin-V binding, caspase-9 and -3 activation, poly (ADPribose) polymerase cleavage, and mitochondrial dysfunction in A549 cells. Moreover, PYR effectively inhibited NSCLC tumour growth in an A549 xenograft model. Conclusion: PYR demonstrated anti-tumour effects on NSCLC in vitro and in vivo, indicating its therapeutic potential against human NSCLC. |
| link: | http://dx.doi.org/10.21873/anticanres.12612 |
| 關聯: | Anticancer Research, v.38, n.6, pp.3435-3445 |
| 顯示於類別: | [藥學系(所)] 期刊論文
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