Zhong Chunge, Wang Shengnan, Jiang Wen-Jie, Li Zexu, Wang Xiaofeng, Fan Shuangshuang, Huang Jun, Wu Hua-Jun, Sheng Ren, Fei Teng
Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China.
Foshan Graduate School of Innovation, Northeastern University, Foshan, 528311, China.
Sci Rep. 2025 Feb 19;15(1):6074. doi: 10.1038/s41598-025-90532-z.
Chemotherapy drug 5-Fluorouracil (5-FU) is a major treatment for many cancers; however, its efficacy is limited by chemoresistance. Here, we investigate the resistance mechanisms to 5-FU and reversal strategies in lung and breast cancer cells. Using multiple 5-FU-resistant lung cancer and breast cancer cell models, we reveal differential cellular and molecular features of 5-FU resistance between different cancer types. We further unravel the implications of immune-related processes, NOTCH and WNT signaling with 5-FU resistance. In lung cancer, the activation of WNT/β-catenin signaling promotes the resistance and blocking this signaling re-sensitizes resistant cells to 5-FU treatment. Our study not only reveals differential features and mechanisms underlying 5-FU resistance across different cancers, but also suggests potential strategies against such resistance.
化疗药物5-氟尿嘧啶（5-FU）是许多癌症的主要治疗方法；然而，其疗效受到化疗耐药性的限制。在这里，我们研究了肺癌和乳腺癌细胞对5-FU的耐药机制及逆转策略。使用多个对5-FU耐药的肺癌和乳腺癌细胞模型，我们揭示了不同癌症类型之间5-FU耐药性的细胞和分子特征差异。我们进一步阐明了免疫相关过程、NOTCH和WNT信号传导与5-FU耐药性的关系。在肺癌中，WNT/β-连环蛋白信号的激活促进了耐药性，阻断该信号可使耐药细胞对5-FU治疗重新敏感。我们的研究不仅揭示了不同癌症中5-FU耐药性的差异特征和机制，还提出了针对这种耐药性的潜在策略。
