Home Neoplasma 2022 Neoplasma Vol.69, No.5, p.1119–1128, 2022

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ISSN 0028-2685
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Neoplasma Vol.69, No.5, p.1119–1128, 2022

Title: Anlotinib inhibits the proliferation and induces apoptosis by inactivating the AKT pathway in androgen receptor-negative prostate cancer cells
Author: Yan Xu, Ji Zheng, Zhi-Ying Ye

Abstract: 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.



Keywords: anlotinib; protein kinase B pathway; prostate cancer; apoptosis; proliferation
Published online: 25-Aug-2022
Year: 2022, Volume: 69, Issue: 5 Page From: 1119, Page To: 1128
doi:10.4149/neo_2022_220624N661
Price: 21.00 €






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