““癌细胞非常聪明，化疗耐药几乎是必然的”

　

顺铂耐药: 一种由多个表观遗传和遗传变化引起的细胞自卫机制

Cisplatin Resistance: A Cellular Self-Defense Mechanism Resulting from Multiple Epigenetic and Genetic Changes

　

翻译：蓝山

                   ——This study clearly implies, cancerous cells are inconceivably smart, resistant to chemo is unavoidable. Poisonous agents can only kill part of the cancer cells, But, impossible to kill all the cancerous cells. 这个研究表明，癌细胞非常聪明，化疗耐药几乎是必然的。毒药可以杀死部分的癌细胞，但是，永远杀不完。

　

顺铂是最有效的广谱抗癌药物之一。它的有效性似乎是由于顺铂的独特性质，它通过多种途径进入细胞，并通过激活或沉默各种不同的基因来启动细胞自我防卫系统，从而引发了大量的表观遗传和/或基因改变。

　

因此，在体内和体外，顺铂耐药在体内和体外的发展，源于复杂的基因表达和蛋白定位改变的复杂基因和表观遗传变化。

　

　

　

广泛发表的证据表明，在对这种有毒金属化合物的耐药性发展过程中经常发现多效性的改变。几乎所有支持细胞存活的机制都发生了变化，包括细胞生长促进途径、细胞凋亡、发育通路、DNA损伤修复和内吞作用。

　

　

　

一般来说，在顺铂耐药细胞中，有几十个基因受到影响，包括铜代谢的通路，以及改变细胞骨架、改变细胞表面蛋白表达和调节上皮间质转移的转录途径。减少积累是导致顺铂耐药最常见的特性之一。这似乎是由于大量的表观遗传和遗传改变导致了细胞表面对顺铂结合位点和或转运体的丧失，以及减少了流体的内吞作用。

　

　

　

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400836/

　

Cisplatin Resistance: A Cellular Self-Defense Mechanism Resulting from Multiple Epigenetic and Genetic Changes
　


Cisplatin is one of the most effective broad-spectrum anticancer drugs. Its effectiveness seems to be due to the unique properties of cisplatin, which enters cells via multiple pathways and forms multiple different DNA-platinum adducts while initiating a cellular self-defense system by activating or silencing a variety of different genes, resulting in dramatic epigenetic and/or genetic alternations. As a result, the development of cisplatin resistance in human cancer cells in vivo and in vitro by necessity stems from bewilderingly complex genetic and epigenetic changes in gene expression and alterations in protein localization. Extensive published evidence has demonstrated that pleiotropic alterations are frequently detected during development of resistance to this toxic metal compound. Changes occur in almost every mechanism supporting cell survival, including cell growth-promoting pathways, apoptosis, developmental pathways, DNA damage repair, and endocytosis. In general, dozens of genes are affected in cisplatin-resistant cells, including pathways involved in copper metabolism as well as transcription pathways that alter the cytoskeleton, change cell surface presentation of proteins, and regulate epithelial-to-mesenchymal transition. Decreased accumulation is one of the most common features resulting in cisplatin resistance. This seems to be a consequence of numerous epigenetic and genetic changes leading to the loss of cell-surface binding sites and/or transporters for cisplatin, and decreased fluid phase endocytosis.