DU145型
蛋白激酶B
细胞生长
细胞凋亡
膜联蛋白
雄激素受体
LNCaP公司
达皮
癌症研究
前列腺癌
PI3K/AKT/mTOR通路
化学
生物
细胞生物学
分子生物学
内科学
癌症
医学
生物化学
作者
Yan Xu,Ji Zheng,Ye Zhiying
出处
期刊:Neoplasma
[AEPress, s.r.o.]
日期:2022-01-01
卷期号:69 (05): 1119-1128
标识
DOI:10.4149/neo_2022_220624n661
摘要
Prostate cancer is one of the most frequently diagnosed cancers in men. The medical treatment of metastatic prostate cancer relies heavily on androgen deprivation. The present study aimed to explore the inhibitory effect of anlotinib on androgen receptor (AR)-negative prostate cancer cell lines in vitro and investigate its mechanism of action. Two prostate cancer cell lines, DU145 and PC-3, were treated with different concentrations (0-80 μM) of anlotinib. Cell proliferation was accessed by CCK-8 assay and EdU staining. Cell nuclear morphology was observed after DAPI staining, cell apoptosis level was evaluated by Annexin-V-FITC/PI staining, and western blot was used to detect the proliferation- and apoptosis-related proteins. The potential interaction between anlotinib and AKT was revealed by molecular docking. After treatment with anlotinib, the cell proliferation rate was significantly inhibited in a dose-dependent manner. The DAPI staining showed that anlotinib could induce apoptosis. Further, Annexin V/PI double staining confirmed the occurrence of apoptosis, accompanied by the increase of cleaved caspase-3 and activated PARP. Moreover, anlotinib significantly decreased the phosphorylation of protein kinase B (AKT) and its downstream pathway proteins in prostate cells (p<0.05). Experiments further confirmed that the activation of the AKT pathway reversed the inhibitory effect of anlotinib on DU145 and PC-3 cell proliferation. In addition, molecular docking analysis revealed potential interactions between anlotinib and AKT1 at multiple sites. Overall, the present study suggested that anlotinib could inhibit the proliferation and induce apoptosis in the AR-negative prostate cancer cell lines, possibly via the inactivation of the AKT pathway.
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