LY3009120 对携带致癌突变的肺癌细胞的抗肿瘤作用。
Antitumor Effects of Pan-RAF Inhibitor LY3009120 Against Lung Cancer Cells Harboring Oncogenic Mutation.
机构信息
Department of General Thoracic, Breast, and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Department of General Thoracic, Breast, and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
出版信息
Anticancer Res. 2020 May;40(5):2667-2673. doi: 10.21873/anticanres.14237.
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.
背景/目的：携带有 BRAF 非 V600E 突变的非小细胞肺癌（NSCLC）患者的治疗策略尚未建立。LY3009120 是一种新发现的泛 RAF 抑制剂，在具有不同 BRAF 基因型的癌症中显示出强大的抗肿瘤作用。本研究旨在探讨 LY3009120 对携带有 BRAF 非 V600E 突变的 NSCLC 细胞的抗肿瘤作用。
材料与方法
通过 MTS 检测和流式细胞术检测 LY3009120 的抗肿瘤作用。通过 Western blot 分析蛋白表达状态。使用小鼠异种移植模型进行体内实验。
结果
LY3009120 抑制了所有检测到的 NSCLC 细胞系中 BRAF 相关下游通路分子的表达，并诱导聚 ADP-核糖聚合酶的切割。LY3009120 还抑制了携带有 BRAF 非 V600E 突变的 NSCLC 细胞的体内肿瘤生长。
结论
LY3009120 是治疗携带有 BRAF 非 V600E 突变的 NSCLC 患者的有效药物。
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