Yan Lili, Liu Yanfen, Huang Yufei, Sun Xiaoyu, Jiang Haiyang, Gu Jie, Xia Jing, Sun Xueni, Sui Xinbing
School of Pharmacy and Department of Medical Oncology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou 311121, China.
Department of Gastrointestinal & Pancreatic Surgery, Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310014, China.
Cancer Biol Med. 2025 Feb 24;22(2):144-65. doi: 10.20892/j.issn.2095-3941.2024.0385.
Erianin has potential anticancer activities, especially against lung cancer. The specific mechanisms underlying the anti-cancer effects, including the molecular targets and signaling pathways in lung cancer, remain poorly understood and necessitate further investigation.
Lung cancer cell viability was evaluated using the CCK-8 assay. Flow cytometry was used to examine the effects of erianin on apoptosis and cell cycle progression. mRNA sequencing and metabolomics analysis were utilized to explore erianin-induced biological changes. Potential targets were identified and validated through molecular docking and Western blot analysis. The roles of mammalian target of rapamycin (mTOR) and carbamoyl-phosphate synthetase/aspartate transcarbamylase/dihydroorotase (CAD) in erianin-induced growth inhibition were studied using gene overexpression/knockdown techniques with uridine and aspartate supplementation confirming pyrimidine metabolism involvement. Additionally, lung cancer-bearing nude mouse models were established to evaluate the anti-lung cancer effects of erianin .
Erianin significantly inhibits the proliferation of lung cancer cells, induces apoptosis, and causes G/M phase cell cycle arrest. Integrative analysis of mRNA sequencing and metabolomics data demonstrated that erianin disrupts pyrimidine metabolism in lung cancer cells. Notably, uridine supplementation mitigated the inhibitory effects of erianin, establishing a connection between pyrimidine metabolism and anticancer activity. Network pharmacology analyses identified mTOR as a key target of erianin. Erianin inhibited mTOR phosphorylation, thereby blocking downstream effectors (S6K and CAD), which are essential regulators of pyrimidine metabolism.
Erianin is a promising therapeutic candidate for lung cancer. Erianin likely inhibits lung cancer cell growth by disrupting pyrimidine metabolism by suppressing mTOR activation.
毛兰素具有潜在的抗癌活性，尤其是对肺癌。其抗癌作用的具体机制，包括肺癌中的分子靶点和信号通路，仍知之甚少，需要进一步研究。
采用CCK-8法评估肺癌细胞活力。流式细胞术用于检测毛兰素对细胞凋亡和细胞周期进程的影响。利用mRNA测序和代谢组学分析来探索毛兰素诱导的生物学变化。通过分子对接和蛋白质免疫印迹分析鉴定并验证潜在靶点。使用基因过表达/敲低技术研究雷帕霉素哺乳动物靶点（mTOR）和氨甲酰磷酸合成酶/天冬氨酸转氨甲酰酶/二氢乳清酸酶（CAD）在毛兰素诱导的生长抑制中的作用，并通过补充尿苷和天冬氨酸来确认嘧啶代谢的参与。此外，建立荷肺癌裸鼠模型以评估毛兰素的抗肺癌作用。
毛兰素显著抑制肺癌细胞增殖，诱导细胞凋亡，并导致G/M期细胞周期阻滞。mRNA测序和代谢组学数据的综合分析表明，毛兰素扰乱肺癌细胞中的嘧啶代谢。值得注意的是，补充尿苷减轻了毛兰素的抑制作用，建立了嘧啶代谢与抗癌活性之间的联系。网络药理学分析确定mTOR是毛兰素的关键靶点。毛兰素抑制mTOR磷酸化，从而阻断下游效应物（S6K和CAD），它们是嘧啶代谢的重要调节因子。
毛兰素是一种有前景的肺癌治疗候选药物。毛兰素可能通过抑制mTOR激活来扰乱嘧啶代谢，从而抑制肺癌细胞生长。
