Sun Peiyuan, Zhang Shuanggou, Qu Yana, Li Xuanyou, Chen Guirui, Wang Xuanjun, Sheng Jun, Wang Jing
Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650201, China; College of Science, Yunnan Agricultural University, Kunming 650201, China.
Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650201, China; College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, China.
Bioorg Chem. 2025 Jan;154:108038. doi: 10.1016/j.bioorg.2024.108038. Epub 2024 Dec 6.
Epidermal growth factor receptor (EGFR) is a starring target for the treatment of non-small cell lung cancer (NSCLC). EGFR tyrosine kinase inhibitors (EGFR-TKIs) have been used to treat NSCLC patients with EGFR-activating mutations. However, most patients invariably develop resistance to these agents due to the occurrence of novel mutations at the EGFR kinase domain. There is an urgent need to develop more effective therapy strategies to provide more selection for patients with NSCLC. Coccinic acid was reported to exerts potential anti-tumor effects, but its mechanism has not been elucidated and warrants investigation. In this study, coccinic acid was shown to inhibit cell proliferation on cells harboring L858R/T790M mutant EGFR by suppressing p-EGFR and p-STAT3. It was also shown that coccinic acid promoted cell cycle distribution and showed a potent apoptosis-inducing efficacy. Further results in vivo assays demonstrated that coccinic acid reduced tumor growth of NCI-H1975 xenograft in nude mice via the EGFR/STAT3 signaling. Moreover, these effects are involving in the binding of coccinic acid to the EGFR extracellular domain. In conclusion, our finding demonstrated that coccinic acid may be utilized as a potential novel candidate for NSCLC with EGFR L858R/T790M mutation.
表皮生长因子受体（EGFR）是治疗非小细胞肺癌（NSCLC）的一个主要靶点。EGFR酪氨酸激酶抑制剂（EGFR-TKIs）已被用于治疗具有EGFR激活突变的NSCLC患者。然而，由于EGFR激酶结构域出现新的突变，大多数患者最终都会对这些药物产生耐药性。迫切需要开发更有效的治疗策略，为NSCLC患者提供更多选择。据报道，球虫酸具有潜在的抗肿瘤作用，但其机制尚未阐明，值得研究。在本研究中，球虫酸通过抑制p-EGFR和p-STAT3，对携带L858R/T790M突变EGFR的细胞具有抑制细胞增殖的作用。还显示球虫酸促进细胞周期分布，并具有强大的诱导凋亡功效。体内试验的进一步结果表明，球虫酸通过EGFR/STAT3信号通路降低了裸鼠中NCI-H1975异种移植瘤的生长。此外，这些作用涉及球虫酸与EGFR细胞外结构域的结合。总之，我们的研究结果表明，球虫酸可能作为具有EGFR L858R/T790M突变的NSCLC的潜在新候选药物。
