Tsaur Igor, Thomas Anita, Monecke Michelle, Zugelder Marion, Rutz Jochen, Grein Timothy, Maxeiner Sebastian, Xie Hui, Chun Felix K-H, Rothweiler Florian, Cinatl Jindrich, Michaelis Martin, Haferkamp Axel, Blaheta Roman A
Department of Urology and Pediatric Urology, University Medicine Mainz, Langenbeckstr. 1, 55131 Mainz, Germany.
Department of Urology, Goethe-University, 60590 Frankfurt am Main, Germany.
Cancers (Basel). 2022 Jun 24;14(13):3111. doi: 10.3390/cancers14133111.
Despite recent advances in the treatment of metastatic prostate cancer (PCa), resistance development after taxane treatments is inevitable, necessitating effective options to combat drug resistance. Previous studies indicated antitumoral properties of the natural compound amygdalin. However, whether amygdalin acts on drug-resistant tumor cells remains questionable. An in vitro study was performed to investigate the influence of amygdalin (10 mg/mL) on the growth of a panel of therapy-naïve and docetaxel- or cabazitaxel-resistant PCa cell lines (PC3, DU145, and LNCaP cells). Tumor growth, proliferation, clonal growth, and cell cycle progression were investigated. The cell cycle regulating proteins (phospho)cdk1, (phospho)cdk2, cyclin A, cyclin B, p21, and p27 and the mammalian target of rapamycin (mTOR) pathway proteins (phospho)Akt, (phospho)Raptor, and (phospho)Rictor as well as integrin β1 and the cytoskeletal proteins vimentin, ezrin, talin, and cytokeratin 8/18 were assessed. Furthermore, chemotactic activity and adhesion to extracellular matrix components were analyzed. Amygdalin dose-dependently inhibited tumor growth and reduced tumor clones in all (parental and resistant) PCa cell lines, accompanied by a G0/G1 phase accumulation. Cell cycle regulating proteins were significantly altered by amygdalin. A moderate influence of amygdalin on tumor cell adhesion and chemotaxis was observed as well, paralleled by modifications of cytoskeletal proteins and the integrin β1 expression level. Amygdalin may, therefore, block tumor growth and disseminative characteristics of taxane-resistant PCa cells. Further studies are warranted to determine amygdalin's value as an antitumor drug.
尽管转移性前列腺癌（PCa）的治疗最近取得了进展，但紫杉烷治疗后耐药性的产生不可避免，因此需要有效的方法来对抗耐药性。先前的研究表明天然化合物苦杏仁苷具有抗肿瘤特性。然而，苦杏仁苷是否作用于耐药肿瘤细胞仍存在疑问。进行了一项体外研究，以研究苦杏仁苷（10 mg/mL）对一组未经治疗以及对多西他赛或卡巴他赛耐药的PCa细胞系（PC3、DU145和LNCaP细胞）生长的影响。研究了肿瘤生长、增殖、克隆生长和细胞周期进程。评估了细胞周期调节蛋白（磷酸化）cdk1、（磷酸化）cdk2、细胞周期蛋白A、细胞周期蛋白B、p21和p27，以及雷帕霉素靶蛋白（mTOR）通路蛋白（磷酸化）Akt、（磷酸化）Raptor和（磷酸化）Rictor，以及整合素β1和细胞骨架蛋白波形蛋白、埃兹蛋白、踝蛋白和细胞角蛋白8/18。此外，还分析了趋化活性和对细胞外基质成分的粘附。苦杏仁苷在所有（亲本和耐药）PCa细胞系中均呈剂量依赖性抑制肿瘤生长并减少肿瘤克隆，同时伴有G0/G1期积累。苦杏仁苷显著改变了细胞周期调节蛋白。还观察到苦杏仁苷对肿瘤细胞粘附和趋化性有适度影响，同时细胞骨架蛋白和整合素β1表达水平也发生了改变。因此，苦杏仁苷可能会阻断紫杉烷耐药PCa细胞的肿瘤生长和扩散特性。有必要进一步研究以确定苦杏仁苷作为抗肿瘤药物的价值。
