Confluence-dependent resistance to cisplatin in lung cancer cells is regulated by transforming growth factor-beta
Confluence-dependent resistance to cisplatin in lung cancer cells is regulated by transforming growth factor-beta
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DOI：
10.3109/01902148.2016.1172370
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发表时间：
2016-01-01
影响因子：
1.7
通讯作者：
Bandoh, Shuji
中科院分区：
文献类型：
--
作者：
Yokokura, Saki;Kanaji, Nobuhiro;Bandoh, Shuji
研究目的：汇合依赖性耐药（CDR）是一种当细胞密度增加时抗癌药物疗效降低的现象。肺癌中的CDR尚未见报道。本研究的目的是探究非小细胞肺癌（NSCLC）细胞中是否会出现CDR，并确定转化生长因子（TGF）-β作为CDR机制的作用。
材料与方法：非小细胞肺癌细胞系A549和H2228在多种细胞密度条件下暴露于顺铂。进行针对TGF -β受体I的RNA干扰以沉默TGF -β通路。
结果：NSCLC细胞中出现了对顺铂的CDR，而未观察到对克唑替尼（一种激活素受体样激酶抑制剂）的CDR。在汇合条件下，培养基中TGF -β1的浓度最高。外源性TGF -β1抑制细胞增殖并降低对顺铂的敏感性。在汇合时，对TGF -β通路的抑制使对顺铂的敏感性增加。
结论：NSCLC细胞中会出现对顺铂的CDR，且TGF -β通路与CDR的调节有关。
Purpose of the Study: Confluence-dependent resistance (CDR) is a phenomenon in which the efficacy of anti-cancer agents decreases when cell density increases. CDR in lung cancer has never been reported. The purpose of this study is to investigate if CDR can occur in NSCLC cells and to find a role for transforming growth factor (TGF)-beta as a mechanism of CDR. Materials and Methods: Non-small cell lung cancer (NSCLC) cell lines A549 and H2228 were exposed to cisplatin in a variety of cell density conditions. RNA interference targeting TGF-beta receptor I was performed to silence the TGF-beta pathway. Results: CDR to cisplatin was induced in NSCLC cells, whereas CDR to crizotinib, an inhibitor of activin receptor-like kinase, was not observed. During confluent conditions, the TGF-beta 1 concentration in the culture medium was the highest. Exogenous TGF-beta 1 inhibited cell proliferation and reduced sensitivity to cisplatin. Inhibition of the TGF-beta pathway increased in terms of sensitivity to cisplatin at confluency. Conclusions: CDR to cisplatin can occur in NSCLC cells, and the TGF-beta pathway is associated with the regulation of CDR.