[Chinese medicinal compound CFF-1 induces the apoptosis and cycle-arrest of prostate cancer cells via the PI3K/AKT/FOXO1 signaling pathway]
| Autor: | Yang, Zhang, Zhao-Meng, Wu, Bo-Han, Lei, Zi-Jie, Lu, Qing-Yi, Zhu, Fu-Song, Xu, Mao-Sen, Zhang, Ping, Liu |
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| Rok vydání: | 2018 |
| Předmět: |
Male
Cell Survival Forkhead Box Protein O1 Cell Cycle Prostatic Neoplasms Apoptosis Antineoplastic Agents Phytogenic Neoplasm Proteins Phosphatidylinositol 3-Kinases Cell Line Tumor Humans Phosphorylation Proto-Oncogene Proteins c-akt Cell Division Cell Proliferation Drugs Chinese Herbal Signal Transduction |
| Zdroj: | Zhonghua nan ke xue = National journal of andrology. 23(9) |
| ISSN: | 1009-3591 |
| Popis: | To explore the apoptosis-inducing effect of the Chinese medicinal compound CFF-1 on prostate cancer cells and its related molecular mechanisms.Normal prostate WPMY-1 cells and prostate cancer LNCaP, CWR22Rv1, PC3 and DU145 cells were treated in dehydrated alcohol with CFF-1 at 0, 2, 5, or 10 mg/ml for 24 hours. Then the viability of the prostate cells was detected by morphological observation, MTT and CCK-8 assay, nuclear condensation and disruption measured by DAPI staining, the cell cycle and apoptosis calculated by flow cytometry, the activity of the PI3K/AKT/FOXO1 signaling pathway and the expressions of its downstream apoptosis- and cycle-related proteins determined by Western blot.CFF-1 significantly arrested the cell cycle in the G1 phase, decreased the cell viability and increased the nuclear condensation and disruption in a dose-dependent manner, and elevated the apoptosis rate of prostate cancer cells. At the molecular level, CFF-1 dose-dependently reduced the activity of the PI3K/AKT signaling pathway and phosphorylation of the FOXO1 protein, increased the transcription activity of FOXO1, and eventually regulated the expressions of cell apoptosis- and cycle-related genes.The Chinese medicinal compound CFF-1 can significantly inhibit the growth, arrest the cycle, and induce the apoptosis of prostate cancer cells by decreasing the activity of the PI3K/AKT/FOXO1 signaling pathway, which suggests its potential clinical application value in the treatment of prostate cancer.目的: 研究复方中药CFF-1诱导前列腺癌细胞的凋亡作用及其相关分子机制的探讨。方法: 通过形态学观察、噻唑蓝（MTT）比色实验、CCK-8实验测定前列腺癌细胞的存活能力；采用DAPI染色法测定细胞核凝缩破裂；运用AnnexinV-FITC/PI双染流式细胞术测定前列腺癌细胞的凋亡率。再通过PI单染流式细胞术测定前列腺癌细胞的周期变化；以及采用蛋白质免疫印迹实验检测PI3K/AKT/FOXO1信号通路以及其下游凋亡相关蛋白和周期相关蛋白的表达。结果: 复方中药CFF-1使前列腺癌细胞周期阻滞在G1期，并呈浓度依赖性降低细胞的存活能力、增加细胞核凝缩破裂以及核小体的形成，显著提高前列腺癌细胞的凋亡率。在分子机制上，CFF-1呈现浓度依赖性下调PI3K/AKT活性，降低FOXO1磷酸化水平，进而上调FOXO1的转录活性，最终影响凋亡相关基因和周期相关基因的表达。结论: CFF-1对前列腺癌细胞的生长有显著的抑制作用，并且通过PI3K/AKT/FOXO1信号通路诱导前列腺癌细胞周期阻滞并发生凋亡，对治疗前列腺癌具有潜在的临床应用价值。. |
| Databáze: | OpenAIRE |
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