Li Haoran, Zhou Dongyuan, Wang Weiquan, Aimaier Reyihanguli, Zhao Haoran, Zhao Heping, Li Jinyu, Pang Xiufeng, Zhou Qian, Zhao Huixin
Xinjiang Key Laboratory of Special Species Conservation and Regulatory Biology, College of Life Science, Xinjiang Normal University, Urumqi, China.
Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing, China.
Probiotics Antimicrob Proteins. 2025 Apr 17. doi: 10.1007/s12602-025-10534-1.
Cyclic lipopeptides secreted by the probiotic bacterium Bacillus subtilis have attracted much attention due to their antitumor activities and low toxicity. However, the role of Mycosubtilin (Myco) in the prevention and treatment of cervical cancer remains unclear. In the present study, we conducted a systematic evaluation of Myco's anti-cervical cancer effects to identify its molecular mechanism of action using proteomics technology. The results reveal that Myco inhibited the growth of HeLa and SiHa cervical cancer cell lines in a dose-dependent (3-15 µg/mL) and time-dependent (12-48 h) manner and significantly reduced colony formation and migration in HeLa cells, highlighting its potential to suppress tumor spread. Moreover, autophagosome and autolysosome numbers were significantly increased after Myco treatment, and the expression of autophagy-related proteins was significantly modulated, suggesting that autophagy plays a role in its anti-cancer mechanism. Myco treatment also induced G1 phase cell cycle arrest in HeLa cells, as confirmed by proteomics analysis. Myco was shown to induce cell cycle arrest in HeLa cells by regulating the P53 pathway and autophagy-dependent cell death via the PI3K/AKT/mTOR signaling pathway, demonstrating its multidimensional effect on cervical cancer cell growths. Myco treatment significantly inhibited tumor growth in vivo in a nude mouse cervical cancer xenograft model, providing direct evidence of its potential as a therapeutic candidate for cervical cancer. Given its unique anti-cancer mechanism and significant therapeutic efficacy, Myco should be considered a promising therapeutic agent for cervical cancer.
益生菌枯草芽孢杆菌分泌的环脂肽因其抗肿瘤活性和低毒性而备受关注。然而，真菌枯草菌素（Myco）在宫颈癌预防和治疗中的作用仍不清楚。在本研究中，我们使用蛋白质组学技术对Myco的抗宫颈癌作用进行了系统评估，以确定其分子作用机制。结果表明，Myco以剂量依赖性（3-15μg/mL）和时间依赖性（12-48小时）的方式抑制HeLa和SiHa宫颈癌细胞系的生长，并显著减少HeLa细胞中的集落形成和迁移，突出了其抑制肿瘤扩散的潜力。此外，Myco处理后自噬体和自溶酶体数量显著增加，自噬相关蛋白的表达也受到显著调节，表明自噬在其抗癌机制中发挥作用。蛋白质组学分析证实，Myco处理还诱导HeLa细胞在G1期细胞周期停滞。结果表明，Myco通过调节P53途径诱导HeLa细胞周期停滞，并通过PI3K/AKT/mTOR信号通路诱导自噬依赖性细胞死亡，证明了其对宫颈癌细胞生长的多维作用。在裸鼠宫颈癌异种移植模型中，Myco处理显著抑制了体内肿瘤生长，为其作为宫颈癌治疗候选药物的潜力提供了直接证据。鉴于其独特的抗癌机制和显著的治疗效果，Myco应被视为一种有前途的宫颈癌治疗药物。
