Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, Shaanxi, China; Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, 710061, Shaanxi, China.
Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, Shaanxi, China.
Chem Biol Interact. 2024 Nov 1;403:111250. doi: 10.1016/j.cbi.2024.111250. Epub 2024 Sep 21.
The incidence of renal cell carcinoma (RCC) is already in the top ten of all types of cancers, with more than 4 %. Epigallocatechin gallate (EGCG), a polyphenolic compound extracted from green tea, has been shown to be effective in the treatment of various tumors. However, limited studies have demonstrated the effect of EGCG on RCC and its underlying molecular mechanisms.
After exposure to gradient concentration (0,5,10,20,40,60,80,100 μM) of EGCG, the cell viability of RCC cells was determined by MTT assay. The migration and invasion abilities of RCC cells were investigated by wound healing and transwell assays. The expression levels of proteins involved in the epithelial-mesenchymal transition (EMT) and autophagy were explored by Western blotting assays. The formation of autophagosome was detected by electron microscope and LC3 puncta assays. Nude mouse xenograft model was used as the model system in vivo.
In the present study, EGCG significantly inhibited the migration, invasion and EMT of RCC cells in a concentrated manner. Further exploration of its mechanism indicated that autophagy is involved in EGCG-mediated metastasis inhibition and EMT inhibition of RCC cells. In addition, EGCG could significantly up-regulate the transcription factor EB (TFEB) and promotes its nuclear localization. The incorporation of TFEB into the nucleus enhanced the transcriptional levels of molecules associated with autophagy. TFEB knockdown inhibited EGCG-mediated autophagy activation, metastasis and EMT inhibition in RCC cells.
In conclusion, these findings demonstrate for the first time that EGCG inhibits migration, invasion, and EMT of RCC by activating TFEB-mediated autophagy. Therefore, the combination of EGCG and TFFB activators or EMT inhibitors is expected to be a promising therapeutic strategy for RCC.
肾细胞癌（RCC）的发病率已经位居所有癌症类型的前 10 位，超过 4%。表没食子儿茶素没食子酸酯（EGCG）是一种从绿茶中提取的多酚化合物，已被证明在治疗各种肿瘤方面有效。然而，有限的研究表明 EGCG 对 RCC 的影响及其潜在的分子机制。
在梯度浓度（0、5、10、20、40、60、80、100 μM）EGCG 暴露后，通过 MTT 测定法测定 RCC 细胞的细胞活力。通过划痕愈合和 Transwell 测定法研究 RCC 细胞的迁移和侵袭能力。通过 Western blot 测定法探讨参与上皮-间充质转化（EMT）和自噬的蛋白质的表达水平。通过电子显微镜和 LC3 斑点测定法检测自噬体的形成。裸鼠异种移植模型作为体内模型系统。
在本研究中，EGCG 显著抑制 RCC 细胞的迁移、侵袭和 EMT，呈浓度依赖性。对其机制的进一步探索表明，自噬参与 EGCG 介导的 RCC 细胞转移抑制和 EMT 抑制。此外，EGCG 可以显著上调转录因子 EB（TFEB）并促进其核定位。TFEB 进入核内增强了与自噬相关的分子的转录水平。TFEB 敲低抑制了 EGCG 介导的 RCC 细胞中的自噬激活、转移和 EMT 抑制。
总之，这些发现首次表明，EGCG 通过激活 TFEB 介导的自噬抑制 RCC 的迁移、侵袭和 EMT。因此，将 EGCG 与 TFFB 激活剂或 EMT 抑制剂联合使用有望成为 RCC 的一种有前途的治疗策略。
