Molecular Mechanisms of Chemoresistance Induced by Cisplatin in NSCLC Cancer Therapy.
Molecular Mechanisms of Chemoresistance Induced by Cisplatin in NSCLC Cancer Therapy.
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DOI：
10.3390/ijms22168885
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发表时间：
2021-08-18
影响因子：
5.6
通讯作者：
Brzeziańska-Lasota E
中科院分区：
文献类型：
--
作者：
Kryczka J;Kryczka J;Czarnecka-Chrebelska KH;Brzeziańska-Lasota E
癌细胞利用多种机制来提高其生存和进展以及抗癌治疗的抵抗力：通过获得生长因子独立性来解除生长调节途径的调节、免疫系统抑制、减少激活T淋巴细胞（拟态）的抗原表达、诱导抗凋亡信号以对抗药物的作用、激活多种DNA修复机制并驱动药物从细胞质中主动流出，以及通过microRNA (miRNA)进行表观遗传调节。由于肺癌通常诊断较晚，因此它仍然是一种主要的恶性肿瘤，五年生存率较低。当确诊时，癌症通常已是晚期，癌细胞可能已经获得了耐药性。本文总结了顺铂耐药的主要机制以及顺铂耐药癌细胞与肿瘤微环境之间的相互作用。它还使用 GSE108214 基因表达综合数据库分析顺铂敏感与顺铂耐药的非小细胞肺癌 (NSCLC) 细胞模型的基因表达谱的变化。它描述了一个蛋白质-蛋白质相互作用网络，表明 TP53、MDM2 和 CDKN1A 基因高度失调，因为它们编码可能与顺铂耐受性相关的顶级网络蛋白，这些蛋白在顺铂耐药细胞中均上调。此外，它通过基于 KEGG 通路分析检查顺铂耐药 NSCLC 细胞中存在的失调通路的多样性，说明了顺铂耐药的多因素性质。
Cancer cells utilise several mechanisms to increase their survival and progression as well as their resistance to anticancer therapy: deregulation of growth regulatory pathways by acquiring grow factor independence, immune system suppression, reducing the expression of antigens activating T lymphocyte cells (mimicry), induction of anti-apoptotic signals to counter the action of drugs, activation of several DNA repair mechanisms and driving the active efflux of drugs from the cell cytoplasm, and epigenetic regulation by microRNAs (miRNAs). Because it is commonly diagnosed late, lung cancer remains a major malignancy with a low five-year survival rate; when diagnosed, the cancer is often highly advanced, and the cancer cells may have acquired drug resistance. This review summarises the main mechanisms involved in cisplatin resistance and interactions between cisplatin-resistant cancer cells and the tumour microenvironment. It also analyses changes in the gene expression profile of cisplatin sensitive vs. cisplatin-resistant non-small cell lung cancer (NSCLC) cellular model using the GSE108214 Gene Expression Omnibus database. It describes a protein-protein interaction network that indicates highly dysregulated TP53, MDM2, and CDKN1A genes as they encode the top networking proteins that may be involved in cisplatin tolerance, these all being upregulated in cisplatin-resistant cells. Furthermore, it illustrates the multifactorial nature of cisplatin resistance by examining the diversity of dysregulated pathways present in cisplatin-resistant NSCLC cells based on KEGG pathway analysis.
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影响因子：
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作者：
Chen MJ;Wu DW;Wang GC;Wang YC;Chen CY;Lee H
通讯作者：
Lee H
影响因子：
11.5
作者：
Ceppi, Paolo;Novello, Silvia;Scagliotti, Giorgio
通讯作者：
Scagliotti, Giorgio
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通讯作者：
Brzeziariska-Lasota, Ewa