Effects of pirfenidone targeting the tumor microenvironment and tumor-stroma interaction as a novel treatment for non-small cell lung cancer
Effects of pirfenidone targeting the tumor microenvironment and tumor-stroma interaction as a novel treatment for non-small cell lung cancer
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DOI：
10.1038/s41598-020-67904-8
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发表时间：
2020-07-02
影响因子：
4.6
通讯作者：
Shintani, Yasushi
中科院分区：
文献类型：
--
作者：
Fujiwara, Ayako;Funaki, Soichiro;Shintani, Yasushi
靶向癌症相关成纤维细胞（CAF）以及基质和癌细胞之间的串扰可能在管理癌症方面具有价值。吡非尼酮（PFD）是一种用于特发性肺纤维化的抗纤维化药物。本研究旨在探讨PFD可能通过抑制成纤维细胞活化和肿瘤-间质相互作用在体外和体内非小细胞肺癌（NSCLC）细胞系中发挥抗肿瘤作用的可能性。PFD显著抑制原代培养的正常人肺成纤维细胞和CAFs的肌成纤维细胞分化和活化。NSCLC细胞与成纤维细胞的条件培养基（CM）共培养改变了形态或上皮间质转化（EMT）状态，PFD抑制了这些变化。CAFs与非小细胞肺癌细胞的CM共培养也诱导CAFs的活化，并且这些变化被PFD抑制。在体内检查中，CAF促进肿瘤进展，PFD抑制肿瘤进展，对肿瘤间质串扰具有抑制作用。PFD不仅可以抑制成纤维细胞的活性，而且可以抑制癌细胞与成纤维细胞之间的相互作用。从多个角度来看，PFD作为NSCLC的一种新型治疗方法可能具有很大的潜力。
Targeting cancer-associated fibroblasts (CAFs), as well as the crosstalk between stroma and cancer cells, could be of value in managing cancers. Pirfenidone (PFD) is an anti-fibrotic agent for idiopathic pulmonary fibrosis. This study aimed to investigate the possibility that PFD might exert an anti-tumor effect through inhibition of fibroblast activation and the tumor-stroma interaction in non-small cell lung cancer (NSCLC) cell lines in vitro and in vivo. PFD significantly inhibited myofibroblast differentiation and activation of both primary cultured normal human lung fibroblasts and CAFs. Cocultivation of NSCLC cells with conditioned media (CM) of fibroblasts changed the morphology or epithelial to mesenchymal transition (EMT) status, and PFD suppressed these changes. Cocultivation of CAFs with CM of NSCLC cells also induced activation of CAFs, and these changes were suppressed by PFD. On in vivo examination, CAFs promoted tumor progression, and PFD suppressed tumor progression with an inhibitory effect on tumor-stroma crosstalk. PFD might inhibit not only fibroblast activity, but also the crosstalk between cancer cells and fibroblasts. PFD may have great potential as a novel treatment for NSCLC from multiple perspectives.