首页> 外文期刊>American Journal of Physiology >Mitochondrial density determines the cellular sensitivity to cisplatin-induced cell death.
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Mitochondrial density determines the cellular sensitivity to cisplatin-induced cell death.

机译:线粒体密度决定了细胞对顺铂诱导的细胞死亡的敏感性。

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We studied the relationship between the mitochondrial density in the cells and the cellular sensitivity to the toxicity of cis-diaminedichloroplatinum II (cisplatin), a potent anticancer agent. Biochemical analyses revealed that the density of mitochondria in the intestinal epithelium changed markedly along its entire length. The density was the highest at the duodenum, medium at the jejunum, and the lowest at the ileum. The sensitivity of epithelial cells to cisplatin toxicity was the highest at the duodenum, medium at the jejunum, and the lowest at the ileum as judged from the occurrence of apoptosis. Similar correlation between the cisplatin sensitivity and mitochondrial density was also observed with in vitro experiments, in which intestinal epithelial cells (IEC-6) and their rho0 cells with reduced number of mitochondria were used. The rho0 cells had a strong resistance to cisplatin compared with the control cells. Cisplatin markedly increased mitochondrial generation of reactive oxygen species inIEC-6 but not in rho0 cells. We analyzed the sensitivity of eight cell lines with different density of mitochondria to cisplatin and found the same positive correlation. These observations clearly show that cellular density of mitochondria is the key factor for the determination of the anticancer activity and side effects of cisplatin.
机译:我们研究了细胞中线粒体密度与细胞对顺式二胺二氯铂II(cisplatin)(一种有效的抗癌药)毒性的敏感性之间的关系。生化分析表明,肠道上皮中线粒体的密度沿其整个长度显着变化。十二指肠的密度最高,空肠的密度最高,回肠的密度最低。根据凋亡的发生情况判断,上皮细胞对顺铂毒性的敏感性在十二指肠最高,在空肠培养基中最高,在回肠最低。在体外实验中,也观察到了顺铂敏感性与线粒体密度之间的相似相关性,其中使用了肠上皮细胞(IEC-6)及其线粒体数量减少的rho0细胞。与对照细胞相比,rho0细胞对顺铂具有很强的抵抗力。在IEC-6中,顺铂显着增加了活性氧的线粒体生成,而在rho0细胞中则没有。我们分析了八种不同线粒体密度的细胞系对顺铂的敏感性,发现相同的正相关。这些观察结果清楚地表明,线粒体的细胞密度是决定顺铂抗癌活性和副作用的关键因素。

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