Jiang Ruqi, Su Guifeng, Chen Xi, Chen Shuo, Li Qianhui, Xie Bumin, Zhao Yang
Department of Obstetrics and Gynecology, Department of Gynecologic Oncology Research Office, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.
Cancer Lett. 2021 Sep 1;521:308-321. doi: 10.1016/j.canlet.2021.08.039.
Endometrial cancer represents one of the most common gynecological tumors in the world. Advanced and relapsed patients rely on drug therapy. Therefore, it is extremely important to seek more effective targeted drugs. This study found that esculetin has an anti-tumor effect on endometrial cancer through cellular proliferation and apoptosis. At the same time, its anti-tumor effect has also been verified in human endometrial cancer xenograft models in nude mice. Western blot results showed that BCLXL, XIAP, and pAKT protein expression level were down-regulated. A pulldown experiment and LC-MS/MS analysis technology revealed that esculetin targets the hnRNPA1 protein. Cellular proliferation experiments following si-hnRNPA1 transfection verified the tumor-promoting effect of hnRNPA1 in endometrial cancer cells. Nuclear and cytoplasmic separation experiment demonstrated esculetin affecting the export of the hnRNPA1/mRNA complex from the nucleus into the cytoplasm. Thus, esculetin targets hnRNPA1, thereby downregulates BCLXL and XIAP mRNA transcription and translation, resulting in apoptosis and an arrest in proliferation.
子宫内膜癌是世界上最常见的妇科肿瘤之一。晚期和复发患者依赖药物治疗。因此，寻找更有效的靶向药物极其重要。本研究发现，七叶亭通过细胞增殖和凋亡对子宫内膜癌具有抗肿瘤作用。同时，其抗肿瘤作用也在裸鼠人子宫内膜癌异种移植模型中得到验证。蛋白质印迹结果显示，BCLXL、XIAP和pAKT蛋白表达水平下调。下拉实验和液相色谱-串联质谱分析技术表明，七叶亭靶向hnRNPA1蛋白。si-hnRNPA1转染后的细胞增殖实验证实了hnRNPA1在子宫内膜癌细胞中的促肿瘤作用。细胞核与细胞质分离实验表明，七叶亭影响hnRNPA1/mRNA复合物从细胞核输出到细胞质。因此，七叶亭靶向hnRNPA1，从而下调BCLXL和XIAP mRNA的转录和翻译，导致细胞凋亡和增殖停滞。
