紫杉醇通过靶向 MUC20 促进食管癌细胞中 mTOR 信号介导的细胞凋亡。
Paclitaxel promotes mTOR signaling-mediated apoptosis in esophageal cancer cells by targeting MUC20.
机构信息
Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
Department of Thoracic Surgery, Shandong Provincial Hospital, Shandong University, Jinan, China.
出版信息
Thorac Cancer. 2023 Nov;14(31):3089-3096. doi: 10.1111/1759-7714.15091. Epub 2023 Sep 29.
BACKGROUND
The aim of this study was to analyze the effect of paclitaxel on the apoptosis of esophageal cancer cells in relation to MUC20.
METHODS
RT-qPCR analysis, a CCK-8 assay, western blotting, and flow cytometry were used to analyze the anticancer effects of paclitaxel treatment or OE-MUC20 in vitro and in vivo.
RESULTS
The in vitro results showed that paclitaxel significantly induced MUC20 upregulation and that paclitaxel treatment or OE-MUC20 significantly decreased esophageal cancer cell viability and increased mTOR signaling activation and apoptosis. In addition, PKM2, a key downstream molecule of mTOR signaling, similarly showed significant upregulation after paclitaxel treatment in cells with OE-MUC20, and its expression was attenuated after treatment with mTOR inhibitors. In a nude mouse model, tumor growth was slow in the OE-MUC20 group and accelerated after inhibition of mTOR signaling.
CONCLUSION
These data suggest that MUC20 is an important target of paclitaxel in esophageal cancer and promotes apoptosis through activation of mTOR signaling.
背景
本研究旨在分析紫杉醇与 MUC20 相关时对食管癌细胞凋亡的影响。
方法
采用 RT-qPCR 分析、CCK-8 检测、Western blot 和流式细胞术分析紫杉醇体外和体内治疗或过表达 MUC20 的抗癌作用。
结果
体外结果表明，紫杉醇显著诱导 MUC20 上调，紫杉醇治疗或过表达 MUC20 显著降低食管癌细胞活力，增加 mTOR 信号激活和细胞凋亡。此外，mTOR 信号的关键下游分子 PKM2 在过表达 MUC20 的细胞中经紫杉醇处理后也显示出明显上调，并且在用 mTOR 抑制剂处理后其表达减弱。在裸鼠模型中，OE-MUC20 组肿瘤生长缓慢，而抑制 mTOR 信号后则加速。
结论
这些数据表明，MUC20 是食管癌中紫杉醇的一个重要靶点，通过激活 mTOR 信号促进细胞凋亡。
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