Anti-cancer chemoagents-triggered centrosome aberrance and its relationship with mitotic cell death in pancreatic cancer cells.

抗癌化学药物引发的中心体异常及其与胰腺癌细胞有丝分裂细胞死亡的关系。

基本信息

批准号：
13671244
负责人：
MIZUMOTO Kazuhiro
金额：
$ 2.24万
依托单位：
Kyushu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671244/
关键词：
centrosome mitotic catastrophe centrosome overduplication cell death pancreatic cancer 放射線照射

项目摘要

Anti-cancer chemotherapy constitutes the major approach of anti-cancer strategy. Such agents act by different mechanisms, but commit a similar cell death process on targeted cells. Centrosome overduplication could be documented as one event involving in radiation-induced cell death. In order to elucidate whether this centrosome abverrance is an unique outcome followed by nuclear DNA damage or a universal phenomenon in relation to cell apoptosis, in this study, we utilized a series of chemo-agents with different mechanism leading treated cells to apoptosis.Human pancreatic cancer cell lines Suit-2 and Capan-2 were used in these experiments. Anti-cancer chemo-agents used in the study included etoposide (VP-16), mitomycin (MMC), cisplatin and 5-fluorouracil (5-FU). Centrosomes were visualized with indirect immunofluorescent microscopy after labeled by special anti-α-tubulin and anti-pericentrin. Cell apoptosis was evaluated by the micronucleus formation and cell death was determined by measuring fluorescence intensity of propidium iodide.All used chemo-agents could cause some degree of centrosome abnormality in the two cell lines, even though distinct profile of the abnormality were present in different cells. VP-16-induced centrosome aberrance was apparently dose dependent. The continuous low dose VP-16 administration (1 μM) caused a marked multi-centrosome abnormality but only moderate cell death in Suit-2 cells. Same continuous treatment with 10 μM of VP-16 in turn resulted in high occurrence of micronuclei formation as well as that of multi-nuclear giant cell formation. We also observed more centrosome number abnormality within these giant cells.The frequent visualizations of multinuclear giant cells and centrosome aberrance provide a strong impression of mitosis failure, which in turn could contribute to mitosis cell death. However, the novel concept of mitosis failure would undergo more intensive investigation.

抗癌化疗构成了抗癌策略的主要方法。这种药物通过不同的机制作用，但在靶向细胞上施加了类似的细胞死亡过程。中心体的过度占用可以记录为涉及辐射引起的细胞死亡的事件。为了阐明这种中心体的依从性是一个独特的结果，随后是核DNA损伤或与细胞凋亡有关的普遍现象，我们在这项研究中使用了一系列具有不同机制的化学药品，导致细胞凋亡导致凋亡引起凋亡。Humanpancreatic pancreatic Calleatical Celline Cell Lines sit-2和Capan-2适用于这些实验，用于这些实验。该研究中使用的抗癌化学药物包括依托泊苷（VP-16），丝裂霉素（MMC），顺铂和5-氟尿嘧啶（5-FU）。通过特殊抗α-微管蛋白和抗肠道蛋白标记后，用间接免疫荧光显微镜可观察中心体。通过微核形成评估凋亡，并通过测量碘化丙啶的荧光强度来确定细胞死亡。所有使用的化学药物都可能导致两种细胞系中的一定程度的中心体异常，即使在不同细胞中存在异常的明显特征。 VP-16诱导的中心体异常显然取决于剂量。连续的低剂量VP-16给药（1μM）引起了明显的多中心异常异常，但仅在西装-2细胞中仅中等细胞死亡。用10μM的VP-16进行相同的连续处理又导致了微核形成以及多核巨细胞形成的形成高。我们还观察到这些巨细胞中的绝对中心数的绝对数量。多核巨细胞和中心异常异常的经常可视化提供了有丝分裂衰竭的强烈印象，这反过来又可能导致有丝分裂细胞死亡。但是，有丝分裂失败的新概念将经历更深入的调查。