Sheng Pan, Chen Zhen, Wen Junjun, Tong Chuanming, Wang Ju, Du Zhengwen
Department of General Surgery, People's Hospital of Dongxihu District, Wuhan 430040, Hubei, China.
Department of Emergency, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430040, Hubei, China.
Bull Cancer. 2025 Feb;112(2):122-134. doi: 10.1016/j.bulcan.2024.11.008. Epub 2024 Dec 31.
Anaplastic thyroid cancer (ATC) is a highly lethal form of thyroid cancer. lysine acetyltransferase 5 (KAT5) has been found to promote ATC development via c-Myc stabilization by previous study. We thus designed experiments to confirm the anti-tumor effect of a KAT5 inhibitor (MG149) in ATC.
Western blotting assessed the level of KAT5, c-Myc, and epithelial-mesenchymal transition (EMT)-related proteins in ATC cells and xenograft tumor tissues. Cell counting kit-8, flow cytometry, wound healing, and transwell assays revealed the effect of MG149 on cell proliferation, apoptosis, migration, and invasion in ATC cell lines. Immunofluorescence detected the level of E-cadherin and N-cadherin in ATC cell lines. The effect of MG149 on KAT5-mediated c-Myc stabilization was detected using co-immunoprecipitation assay. Tumor volume and tumor weight in ATC xenograft models were evaluated. H&E staining showed the effect of MG149 on lung metastasis in vivo. We further investigated whether MG149 can enhance the sensitivity of ATC to cisplatin (CDDP).
MG149 inhibited cell proliferation and increased the apoptosis of cells. MG149 suppressed the migratory and invasive ability of ATC cells. The EMT in CAL-62 and 8505C cells was significantly inhibited by MG149. MG149 suppressed the KAT5-mediated c-Myc acetylation. MG149 inhibited tumor growth and lung metastasis in vivo. Additionally, MG149 potentiated the sensitivity to CDDP in ATC cells in vitro and in vivo.
MG149 suppresses ATC progression and metastasis by inhibiting the acetylation of c-Myc mediated by KAT5.
间变性甲状腺癌（ATC）是一种具有高度致死性的甲状腺癌形式。先前的研究发现赖氨酸乙酰转移酶5（KAT5）通过稳定c-Myc促进ATC的发展。因此，我们设计实验来证实KAT5抑制剂（MG149）对ATC的抗肿瘤作用。
蛋白质免疫印迹法评估ATC细胞和异种移植瘤组织中KAT5、c-Myc和上皮-间质转化（EMT）相关蛋白的水平。细胞计数试剂盒-8、流式细胞术、伤口愈合实验和Transwell实验揭示了MG149对ATC细胞系中细胞增殖、凋亡、迁移和侵袭的影响。免疫荧光检测ATC细胞系中E-钙黏蛋白和N-钙黏蛋白的水平。使用免疫共沉淀实验检测MG149对KAT5介导的c-Myc稳定化的影响。评估ATC异种移植模型中的肿瘤体积和肿瘤重量。苏木精-伊红染色显示MG149对体内肺转移的影响。我们进一步研究了MG149是否能增强ATC对顺铂（CDDP）的敏感性。
MG149抑制细胞增殖并增加细胞凋亡。MG149抑制ATC细胞的迁移和侵袭能力。MG149显著抑制CAL-62和8505C细胞中的EMT。MG149抑制KAT5介导的c-Myc乙酰化。MG149在体内抑制肿瘤生长和肺转移。此外，MG149在体外和体内均增强了ATC细胞对CDDP的敏感性。
MG149通过抑制KAT5介导的c-Myc乙酰化来抑制ATC的进展和转移。
