Extracts of European mistletoe (Viscum album) are popular as a complementary treatment for patients with many different cancer types. However, whether these extracts actually block bladder cancer progression remains unknown. The influence of different mistletoe extracts on bladder cancer cell growth and proliferation was investigated by exposing RT112, UMUC3, and TCCSup cells to mistletoe from hawthorn (Crataegi), lime trees (Tiliae), willow trees (Salicis), or poplar trees (Populi). The tumor cell growth and proliferation, apoptosis induction, and cell cycle progression were then evaluated. Alterations in integrin α and β subtype expression as well as CD44 standard (CD44s) and CD44 variant (CD44v) expressions were evaluated. Cell cycle-regulating proteins (CDK1 and 2, Cyclin A and B) were also investigated. Blocking and knock-down studies served to correlate protein alterations with cell growth. All extracts significantly down-regulated the growth and proliferation of all bladder cancer cell lines, most strongly in RT112 and UMUC3 cells. Alterations in CD44 expression were not homogeneous but rather depended on the extract and the cell line. Integrin α3 was, likewise, differently modified. Integrin α5 was diminished in RT112 and UMUC3 cells (significantly) and TCCSup (trend) byPopuliandSalicis.PopuliandSalicisarrested UMUC3 in G0/G1 to a similar extent, whereas apoptosis was induced most efficiently bySalicis. Examination of cell cycle-regulating proteins revealed down-regulation of CDK1 and 2 and Cyclin A bySalicisbut down-regulation of CDK2 and Cyclin A byPopuli. Blocking and knock-down studies pointed to the influence of integrin α5, CD44, and the Cyclin–CDK axis in regulating bladder cancer growth. Mistletoe extracts do block bladder cancer growth in vitro, with the molecular action differing according to the cell line and the host tree of the mistletoe. Integrating mistletoe into a guideline-based treatment regimen might optimize bladder cancer therapy.
欧洲槲寄生提取物作为多种癌症类型的补充疗法广受欢迎。然而，这些提取物是否确实能抑制膀胱癌进展尚不明确。本研究通过将RT112、UMUC3和TCCSup细胞分别暴露于源自山楂树、椴树、柳树或杨树的槲寄生提取物，探究不同槲寄生提取物对膀胱癌细胞生长与增殖的影响。随后评估了肿瘤细胞生长增殖、凋亡诱导及细胞周期进程的变化，并检测整合素α/β亚型表达以及CD44标准型（CD44s）与变异型（CD44v）表达的改变，同时考察细胞周期调控蛋白（CDK1/2、Cyclin A/B）的表达情况。通过阻断与敲低实验验证蛋白改变与细胞生长的相关性。 结果显示：所有提取物均显著抑制各膀胱癌细胞系的生长增殖，其中对RT112和UMUC3细胞的抑制作用最强。CD44表达变化呈现非均质性，其改变模式取决于提取物种类与细胞系类型。整合素α3的表达同样呈现差异性改变。杨树与柳树提取物能显著降低RT112和UMUC3细胞的整合素α5表达（TCCSup细胞亦呈下降趋势）。柳树与杨树提取物对UMUC3细胞G0/G1期阻滞程度相近，但柳树提取物诱导凋亡的效果最为显著。细胞周期调控蛋白检测显示：柳树提取物下调CDK1/2及Cyclin A表达，而杨树提取物主要下调CDK2与Cyclin A。阻断与敲低实验证实整合素α5、CD44及Cyclin-CDK轴在调控膀胱癌生长中具有重要作用。 结论：槲寄生提取物在体外确实能抑制膀胱癌生长，其分子作用机制因细胞系及槲寄生宿主树种而异。将槲寄生整合至基于指南的治疗方案中，可能优化膀胱癌的临床治疗策略。
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