Xiong Kangping, Wang Gang, Peng Tianchen, Zhou Fenfang, Chen Siming, Liu Wei, Ju Lingao, Xiao Yu, Qian Kaiyu, Wang Xinghuan
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China.
Cancer Cell Int. 2021 Aug 30;21(1):461. doi: 10.1186/s12935-021-02175-5.
New effective drugs for prostate cancer (PCa) treatment are urgently needed. Avasimibe was recently identified as a promising drug for anticancer therapies. The main purpose of this study was to explore the effects and the underlying mechanisms of avasimibe in prostate cancer.
In this study, MTT and clonogenic survival assays were performed to detect cell proliferation after avasimibe treatment. The effect of avasimibe on cell migration was measured by wound healing and transwell migration assays. Cell cycle distribution and apoptosis were detected by flow cytometry. Immunofluorescence staining and western blot analysis were used to detect the expression of cell cycle-related proteins and epithelial-mesenchymal transition (EMT)-related proteins. In vivo, the antitumour effects of avasimibe were evaluated using a xenograft model and pulmonary metastasis model.
The study found that avasimibe suppresses tumour growth and triggers G1 phase arrest. Moreover, the expression of the cell cycle-related proteins CDK2/4/6, Cyclin D1 and Cyclin A1 + A2 was significantly increased and p21 expression was decreased after avasimibe treatment. The migration of PCa cells was attenuated after treatment with avasimibe, followed by the downregulation of the expression of the EMT-related proteins N-cadherin, β-catenin, vimentin, Snail and MMP9 and upregulation of E-cadherin expression. Moreover, E2F-1 was elevated after treatment with avasimibe. After knockdown of E2F-1 expression, the inhibition of cell proliferation and migration caused by avasimibe was significantly recovered. The results of the xenograft model showed that avasimibe suppressed tumour growth in vivo. Immunofluorescence staining revealed lower levels of Ki67 and higher levels of E2F-1 in tumour tissues of the avasimibe group than those of the control group. A pulmonary metastasis model also confirmed the inhibition of PCa metastasis by avasimibe. The number of lung metastatic foci in the avasimibe group was significantly decreased compared with that in the control group.
Our results suggest that avasimibe can suppress tumour proliferation and metastasis via the E2F-1 signalling pathway. These findings demonstrate the potential of avasimibe as a new effective drug for PCa treatment.
前列腺癌（PCa）治疗急需新型有效药物。阿伐西丁最近被确定为一种有前景的抗癌治疗药物。本研究的主要目的是探讨阿伐西丁对前列腺癌的作用及其潜在机制。
在本研究中，进行MTT和克隆形成存活试验以检测阿伐西丁处理后的细胞增殖。通过伤口愈合和Transwell迁移试验测量阿伐西丁对细胞迁移的影响。通过流式细胞术检测细胞周期分布和凋亡。免疫荧光染色和蛋白质印迹分析用于检测细胞周期相关蛋白和上皮-间质转化（EMT）相关蛋白的表达。在体内，使用异种移植模型和肺转移模型评估阿伐西丁的抗肿瘤作用。
研究发现阿伐西丁抑制肿瘤生长并引发G1期阻滞。此外，阿伐西丁处理后，细胞周期相关蛋白CDK2/4/6、细胞周期蛋白D1和细胞周期蛋白A1+A2的表达显著增加，而p21表达降低。阿伐西丁处理后，PCa细胞的迁移减弱，随后EMT相关蛋白N-钙黏蛋白、β-连环蛋白、波形蛋白、Snail和MMP9的表达下调，E-钙黏蛋白表达上调。此外，阿伐西丁处理后E2F-1升高。敲低E2F-1表达后，阿伐西丁对细胞增殖和迁移的抑制作用显著恢复。异种移植模型的结果表明阿伐西丁在体内抑制肿瘤生长。免疫荧光染色显示，阿伐西丁组肿瘤组织中Ki67水平低于对照组，E2F-1水平高于对照组。肺转移模型也证实了阿伐西丁对PCa转移的抑制作用。与对照组相比，阿伐西丁组肺转移灶数量显著减少。
我们的结果表明，阿伐西丁可通过E2F-1信号通路抑制肿瘤增殖和转移。这些发现证明了阿伐西丁作为一种新型有效PCa治疗药物的潜力。
