Department of General, Visceral and Transplantation Surgery, Hannover Medical School, Hannover, Germany.
BMC Cancer. 2012 Oct 11;12:466. doi: 10.1186/1471-2407-12-466.
Cholangiocarcinoma (CC) is a primary liver cancer with increasing incidence worldwide. Despite all efforts made in past years, prognosis remains to be poor. At least in part, this might be explained by a pronounced resistance of CC cells to undergo apoptosis. Thus, new therapeutic strategies are imperatively required. In this study we investigated the effect of Salinomycin, a polyether ionophore antibiotic, on CC cells as an appropriate agent to treat CC. Salinomycin was quite recently identified to induce apoptosis in cancer stem cells and to overcome apoptosis-resistance in several leukemia-cells and other cancer cell lines of different origin.
To delineate the effects of Salinomycin on CC, we established an in vitro cell culture model using three different human CC cell lines. After treatment apoptosis as well as migration and proliferation behavior was assessed and additional cell cycle analyses were performed by flowcytometry.
By demonstrating Annexin V and TUNEL positivity of human CC cells, we provide evidence that Salinomycin reveals the capacity to break apoptosis-resistance in CC cells. Furthermore, we are able to demonstrate that the non-apoptotic cell fraction is characterized by sustainable impaired migration and proliferation. Cell cycle analyses revealed G2-phase accumulation of human CC cells after treatment with Salinomycin. Even though apoptosis is induced in two of three cell lines of CC cells, one cell line remained unaffected in regard of apoptosis but revealed as the other CC cells decreased proliferation and migration.
In this study, we are able to demonstrate that Salinomycin is an effective agent against previously resistant CC cells and might be a potential candidate for the treatment of CC in the future.
胆管癌（CC）是一种原发性肝癌，其全球发病率呈上升趋势。尽管过去几年做出了种种努力，但其预后仍较差。至少部分原因可能是 CC 细胞对凋亡的明显抵抗。因此，迫切需要新的治疗策略。在这项研究中，我们研究了盐霉素（一种聚醚离子载体抗生素）对 CC 细胞的作用，将其作为治疗 CC 的合适药物。最近发现盐霉素可诱导癌症干细胞凋亡，并克服几种白血病细胞和其他不同来源的癌细胞系中的凋亡抵抗。
为了描绘盐霉素对 CC 的影响，我们建立了一种体外细胞培养模型，使用三种不同的人 CC 细胞系。在治疗后，评估凋亡以及迁移和增殖行为，并通过流式细胞术进行额外的细胞周期分析。
通过证明人 CC 细胞的 Annexin V 和 TUNEL 阳性，我们提供了盐霉素能够打破 CC 细胞凋亡抵抗的证据。此外，我们能够证明非凋亡细胞部分的特征是持续受损的迁移和增殖。细胞周期分析显示，盐霉素处理后人 CC 细胞的 G2 期积累。尽管三种 CC 细胞系中有两种细胞系诱导了凋亡，但有一种细胞系在凋亡方面不受影响，但与其他 CC 细胞相比，增殖和迁移减少。
在这项研究中，我们能够证明盐霉素是一种针对先前耐药的 CC 细胞的有效药物，并且可能是未来治疗 CC 的潜在候选药物。
