已发表论文

苦豆碱通过在前列腺癌中诱导细胞凋亡和细胞周期停滞而实现在体外和体内的抗肿瘤作用

 

Authors Ling Z, Guan H, You Z, Wang C, Hu L, Zhang L, Wang Y, Chen S, Xu B, Chen M

Received 11 February 2018

Accepted for publication 27 March 2018

Published 11 May 2018 Volume 2018:11 Pages 2735—2743

DOI https://doi.org/10.2147/OTT.S165262

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Justinn Cochran

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Geoffrey Pietersz

Background: Prostate cancer (PCa) is one of the most common malignant diseases among male patients. Although androgen deprivation therapy remains the main treatment for PCa, most patients would inevitably progress to castration-resistant PCa, which is the main cause of cancer-related deaths. Thus, novel antitumor agents are urgently needed. Recent studies demonstrated that aloperine (ALO) as a natural alkaloid showed antitumor effects in other cancer types. However, the biological function and underlying mechanisms of ALO in PCa have not been investigated.
Methods: PCa cell lines including LNCaP, PC3 and DU145 were cultured and treated with ALO. Cell Counting Kit-8 assay, colony formation assay, apoptosis assay and cell cycle assay were conducted to assess the biological role of ALO. In addition, a PCa subcutaneous xenograft mouse model was established to evaluate the role of ALO in terms of proliferation and apoptosis in vivo. We further measured the protein expression levels of p-Akt/Akt, p-ERK/ERK, c-Myc, cleaved caspase 3, p21, p53, Bcl-2 and Bax using the Western blot 48 h after ALO treatment of PCa cells.
Results: ALO effectively inhibited the cell viability of PCa by inducing cell cycle arrest via the activation of the p53/p21 pathway and triggering apoptosis in vitro and in vivo. ALO also inhibited phosphorylation of Akt and ERK protein kinases and activated cleaved caspase 3 while exerting antiproliferation function through inducing apoptosis and cell cycle arrest in PCa cells.
Conclusion: Based on our findings, we conclude that ALO could suppress the tumor growth and promote cell apoptosis and cell cycle arrest in PCa cells, which indicated that ALO could act as a novel therapeutic agent in treatment of human PCa.
Keywords: aloperine, prostate cancer, proliferation, apoptosis, cell cycle