Inhibition of Prostate Cancer DU-145 Cells Proliferation by Anthopleura anjunae Oligopeptide (YVPGP) via PI3K/AKT/mTOR Signaling Pathway.
Inhibition of Prostate Cancer DU-145 Cells Proliferation by Anthopleura anjunae Oligopeptide (YVPGP) via PI3K/AKT/mTOR Signaling Pathway.
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Anthopleura anjunae 寡肽 (YVPGP) 通过 PI3K/AKT/mTOR 信号通路抑制前列腺癌 DU-145 细胞增殖
DOI：
10.3390/md16090325
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发表时间：
2018-09-11
期刊：
影响因子：
5.4
通讯作者：
Ding G
中科院分区：
文献类型：
--
作者：
Li X;Tang Y;Yu F;Sun Y;Huang F;Chen Y;Yang Z;Ding G
我们在体外和体内研究了Anthopleura anjunae寡肽（AAP-H， YVPGP）对前列腺癌DU-145细胞的抗肿瘤作用机制。结果表明，AAP-H无毒且具有抗肿瘤活性。细胞周期分析表明，AAP-H可能在S期阻滞DU-145细胞。研究磷脂酰肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白（PI3K/AKT/mTOR）信号通路在APP-H抗肿瘤机制中的作用。结果显示，AAP-H处理导致p-AKT （Ser473）、p-PI3K （p85）和p-mTOR （Ser2448）水平呈剂量依赖性降低，而与未处理的DU-145细胞相比，t-AKT和t-PI3K水平保持不变。LY294002 （10 μM）或雷帕霉素（20 nM）抑制DU-145细胞PI3K/AKT/mTOR信号通路，可有效减弱aap - h诱导的AKT和mTOR磷酸化。同时，抑制剂的加入进一步提高了aap - h诱导的裂解caspase-3水平。此外，我们还研究了AAP-H在裸鼠模型中对肿瘤生长的影响以及PI3K/AKT/mTOR信号通路的作用。免疫组化分析显示，DU-145异种移植物中活化的AKT、PI3K和mTOR水平降低。Western blotting显示，AAP-H处理导致p-AKT （Ser473）、p-PI3K （p85）和p-mTOR （Ser2448）水平呈剂量依赖性降低，而t-AKT和t-PI3K水平保持不变。同样，AAP-H处理后，Bcl-xL水平降低，Bax水平升高。AAP-H还增加了引发体（caspase 8和9）和执行体（caspase 3和7）的水平。因此，APP-H对DU-145细胞的抗肿瘤机制可能是通过调控PI3K/AKT/mTOR信号通路，最终通过线粒体和死亡受体途径促进细胞凋亡。因此，疏水寡肽（YVPGP）可作为预防或治疗前列腺癌的佐剂在未来发展。
We investigated the antitumor mechanism of Anthopleura anjunae oligopeptide (AAP-H, YVPGP) in prostate cancer DU-145 cells in vitro and in vivo. Results indicated that AAP-H was nontoxic and exhibited antitumor activities. Cell cycle analysis indicated that AAP-H may arrest DU-145 cells in the S phase. The role of the phosphatidylinositol 3-kinase/protein kinase B/mammalian rapamycin target protein (PI3K/AKT/mTOR) signaling pathway in the antitumor mechanism of APP-H was investigated. Results showed that AAP-H treatment led to dose-dependent reduction in the levels of p-AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448), whereas t-AKT and t-PI3K levels remained unaltered compared to the untreated DU-145 cells. Inhibition of PI3K/AKT/mTOR signaling pathway in the DU-145 cells by employing inhibitor LY294002 (10 μM) or rapamycin (20 nM) effectively attenuated AAP-H-induced phosphorylation of AKT and mTOR. At the same time, inhibitor addition further elevated AAP-H-induced cleaved-caspase-3 levels. Furthermore, the effect of AAP-H on tumor growth and the role of the PI3K/AKT/mTOR signaling pathway in nude mouse model were also investigated. Immunohistochemical analysis showed that activated AKT, PI3K, and mTOR levels were reduced in DU-145 xenografts. Western blotting showed that AAP-H treatment resulted in dose-dependent reduction in p-AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448) levels, whereas t-AKT and t-PI3K levels remained unaltered. Similarly, Bcl-xL levels decreased, whereas that of Bax increased after AAP-H treatment. AAP-H also increased initiator (caspase 8 and 9) and executor caspase (caspase 3 and 7) levels. Therefore, the antitumor mechanism of APP-H on DU-145 cells may involve regulation of the PI3K/AKT/mTOR signaling pathway, which eventually promotes apoptosis via mitochondrial and death receptor pathways. Thus, the hydrophobic oligopeptide (YVPGP) can be developed as an adjuvant for the prevention or treatment of prostate cancer in the future.
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影响因子：
11.2
作者：
Chen, Kuen-Feng;Yeh, Pei-Yen;Cheng, Ann-Lii
通讯作者：
Cheng, Ann-Lii
影响因子：
3.9
作者：
Knight, Z. A.;Shokat, K. M.
通讯作者：
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影响因子：
2.9
作者：
Feng, Li-Min;Wang, Xue-Feng;Huang, Qing-Xian
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影响因子：
45.3
作者：
Atkins, MB;Hidalgo, M;Sherman, ML
通讯作者：
Sherman, ML
影响因子：
4.5
作者：
Hager, Martina;Haufe, Heike;Moser, Patrizia L.
通讯作者：
Moser, Patrizia L.