Antitumor Effects of Pan-RAF Inhibitor LY3009120 Against Lung Cancer Cells Harboring Oncogenic BRAF Mutation
Antitumor Effects of Pan-RAF Inhibitor LY3009120 Against Lung Cancer Cells Harboring Oncogenic BRAF Mutation
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DOI：
10.21873/anticanres.14237
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发表时间：
2020-05-01
影响因子：
2
通讯作者：
Toyooka, Shinichi
中科院分区：
文献类型：
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作者：
Miyauchi, Shunsaku;Shien, Kazuhiko;Toyooka, Shinichi
背景/目的：携带BRAF非V600E突变的非小细胞肺癌（NSCLC）患者的治疗策略尚未确定。LY3009120是一种新发现的泛RAF抑制剂，在各种BRAF基因型的癌症中显示出强大的抗肿瘤作用。本研究研究了LY3009120在携带BRAF非V600E突变的NSCLC细胞中的抗肿瘤作用。材料与方法：采用MTS法和流式细胞术检测LY3009120的抗肿瘤作用。蛋白质印迹分析蛋白质的表达状态。将小鼠异种移植模型用于体内实验。结果如下：LY3009120抑制BRAF相关下游通路分子，并诱导所有检查的NSCLC细胞系中聚ADP-核糖聚合酶的裂解。LY3009120还抑制携带BRAF非V600E突变的NSCLC细胞的体内肿瘤生长。结论：LY3009120是治疗BRAF非V600E突变型NSCLC的有效药物。
Background/Aim: The therapeutic strategy for patients with non-small-cell lung cancer (NSCLC) harboring the BRAF non-V600E mutation has not been established. LY3009120, a newly discovered pan-RAF inhibitor, has shown strong antitumor effects in cancers with various BRAF genotypes. This study investigated the antitumor effects of LY3009120 in NSCLC cells harboring the BRAF non-V600E mutation. Materials and Methods: We examined the antitumor effects of LY3009120 by MTS assay and flow cytometry. We analyzed the expression status of proteins by western blot. The mouse xenograft models were used for the in vivo experiments. Results: LY3009120 suppressed BRAF-related downstream pathway molecules and induced cleavage of poly ADP-ribose polymerase in all examined NSCLC cell lines. LY3009120 also inhibited in vivo tumor growth in NSCLC cells harboring the BRAF non-V600E mutation. Conclusion: LY3009120 is a potent therapeutic agent for patients with BRAF non-V600E mutant NSCLC.