Liu Jinlong, Xu Mengran, Han Liu, Rao Yuxuan, Han Haoming, Zheng Haoran, Wu Jinying, Sun Xin
School of Pharmaceutical Sciences, Jilin Medical University, No. 5, Jilin Street, Fengman District, Jilin 132013, China.
Pharmaceuticals (Basel). 2025 Jul 12;18(7):1036. doi: 10.3390/ph18071036.
The mechanisms underlying the metastasis of non-small-cell lung cancer (NSCLC) have long been a focal point of medical research. The anti-tumor effects of chelerythrine (CHE) have been confirmed; however, its ability to inhibit tumor metastasis and the underlying mechanisms remain unknown. The aim of this study was to investigate the inhibitory effects and molecular mechanisms of CHE on transforming growth factor-beta (TGF-β)-induced epithelial-mesenchymal transition (EMT). : Wound healing and Transwell assays were employed to evaluate TGF-β-induced migration in A549 cells and the inhibitory effects of CHE. Ribonucleotide reductase subunit M2 (RRM2) expression levels were detected via Western blot and immunofluorescence staining. Western blot and RT-qPCR were used to examine the expression levels of EMT-related markers. Animal experiments were conducted to analyze the role of RRM2 in the CHE inhibition of TGF-β-induced lung cancer metastasis. : This study found that TGF-β treatment enhanced the metastasis of A549 cells, while CHE inhibited the expression of TGF-β-induced EMT-related transcription factors by RRM2, thereby suppressing tumor cell migration ( < 0.05). Furthermore, the oral administration of CHE inhibited the metastasis of A549 cells to the lungs from the tail vein in mice, consistent with in vitro findings. Despite the high doses of CHE used, there was no evidence of toxicity. : Our data reveal the mechanism of the anti-metastatic effects of CHE on TGF-β-induced EMT and indicate that CHE can be used as an effective anti-tumor treatment.
非小细胞肺癌（NSCLC）转移的潜在机制长期以来一直是医学研究的重点。白屈菜红碱（CHE）的抗肿瘤作用已得到证实；然而，其抑制肿瘤转移的能力及潜在机制仍不清楚。本研究旨在探讨CHE对转化生长因子-β（TGF-β）诱导的上皮-间质转化（EMT）的抑制作用及其分子机制。采用伤口愈合实验和Transwell实验评估TGF-β诱导的A549细胞迁移及CHE的抑制作用。通过蛋白质免疫印迹法和免疫荧光染色检测核糖核苷酸还原酶亚基M2（RRM2）的表达水平。采用蛋白质免疫印迹法和RT-qPCR检测EMT相关标志物的表达水平。进行动物实验以分析RRM2在CHE抑制TGF-β诱导的肺癌转移中的作用。本研究发现，TGF-β处理增强了A549细胞的转移，而CHE通过RRM2抑制TGF-β诱导的EMT相关转录因子的表达，从而抑制肿瘤细胞迁移（P<0.05）。此外，口服CHE可抑制A549细胞从尾静脉转移至小鼠肺部，这与体外实验结果一致。尽管使用了高剂量的CHE，但未发现毒性证据。我们的数据揭示了CHE对TGF-β诱导的EMT的抗转移作用机制，并表明CHE可作为一种有效的抗肿瘤治疗药物。
