期刊
EXPERIMENTAL AND THERAPEUTIC MEDICINE
卷 11, 期 2, 页码 613-618出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/etm.2015.2915
关键词
fangchinoline; lung cancer; cell cycle; retinoblastoma; cyclin D1
资金
- Jiangsu Province Health Department [J201410]
- Yangzhou Vocational College of Environment and Resources
Fangchinoline (Fan) is a bioactive compound isolated from the Chinese herb Stephania tetrandra S. Moore (Fen Fang Ji). The aim of the present study was to investigate the effect of Fan on the proliferation of SPC-A-1 lung cancer cells, and to define the associated molecular mechanisms. Following treatment with Fan, Cell Counting Kit-8, phase contrast imaging and Giemsa staining assays were used to detect cell viability; flow cytometry was performed to analyze the cell cycle distribution; and reverse transcription-quantitative polymerase chain reaction and western blot assays were used to investigate changes in the expression levels of cell cycle-associated genes and proteins. In the present study, treatment with Fan markedly inhibited the proliferation of SPC-A-1 lung cancer cells and significantly increased the percentage of cells in the G(0)/G(1) phase of the cell cycle in a dose-dependent manner (P<0.05 for 2.5-5 mu m; P<0.01 for 10 mu m), whereas the percentage of cells in the S and G(2)/M phases were significantly reduced following treatment (P<0.05 for 5 mu m; P<0.01 for 10 mu m). Mechanistically, Fan significantly reduced the mRNA expression levels of cyclin D1, cyclin-dependent kinase 4 (CDK4) and CDK6 (P<0.05 for 2.5-5 mu m; P<0.01 for 10 mu m), which are key genes in the regulation of the G(0)/G(1) phase of the cell cycle. Furthermore, treatment with Fan also decreased the expression of phosphorylated retinoblastoma (Rb) and E2F transcription factor-1 (E2F-1) proteins (P<0.05 for 5 mu m; P<0.01 for 10 mu m). In summary, the present study demonstrated that Fan inhibited the proliferation of SPC-A-1 lung cancer cells and induced cell cycle arrest at the G(0)/G(1) phase. These effects may be mediated by the downregulation of cellular CDK4, CDK6 and cyclin D1 levels, thus leading to hypophosphorylation of Rb and subsequent suppression of E2F-1 activity. Therefore, the present results suggest that Fan may be a potential drug candidate for the prevention of lung cancer.
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