Neighbors' death is required for surviving human adenocarcinoma PC-9 cells in an early stage of gefitinib treatment
Neighbors' death is required for surviving human adenocarcinoma PC-9 cells in an early stage of gefitinib treatment
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DOI：
10.1016/j.bbrc.2016.09.092
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发表时间：
2016-10-14
影响因子：
3.1
通讯作者：
Hohjoh, Hirohiko
中科院分区：
文献类型：
--
作者：
Takahashi, Masaki;Fukuoka, Masashi;Hohjoh, Hirohiko
获得性耐药是化疗中的一个主要问题，了解幼稚细胞首次接触药物时保护自己免受药物伤害的机制，可能会提供问题的解决方案。吉非替尼是一种表皮生长因子受体(EGFR)酪氨酸激酶抑制剂，被用作抗癌药物；然而，吉非替尼治疗有时可能会导致癌细胞逐渐对吉非替尼产生耐药。在这里，我们描述了即使在吉非替尼存在的情况下，人腺癌PC-9细胞也能够通过激活涉及成纤维细胞生长因子受体(FGFR)及其信号分子FGF2的另一条信号通路而存活下来，并进一步提示，启动该通路的FGF2可能来自被吉非替尼杀死的邻近细胞，即在吉非替尼治疗的早期，这种存活可能建立在邻居牺牲的基础上。我们的发现提示，在吉非替尼治疗后不久，细胞是否有机会遇到FGF2等生存因子可能是细胞存活和获得吉非替尼耐受性的重要十字路口。(C)2016 Elsevier Inc.保留所有权利。
Acquired drug resistance is a major problem in chemotherapy, and understanding of the mechanism, by which naive cells defend themselves from drugs when the cells exposed to the drugs for the first time, may provide a solution of the problem. Gefitinib is an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, and used as an anticancer drug; however, gefitinib treatment may sometimes lead cancer cells gradually into a gefitinib-tolerance. Here we describe that human adenocarcinoma PC-9 cells even under the presence of gefitinib were able to survive by activating another signaling pathway involving fibroblast growth factor receptor (FGFR) and its signaling molecule, FGF2; and further suggest that the FGF2 for initiating the pathway might be supplied from neighboring cells which were killed by gefitinib, i.e., the survival might be founded on neighbors' sacrifice in an early stage of gefitinib treatment. Our findings suggested that whether cells had a chance to encounter to survival factors such as FGF2 soon after gefitinib treatment might be an important crossroads for the cells for survival and for gaining a gefitinib tolerance. (C) 2016 Elsevier Inc. All rights reserved.