Human cervical cancer is the fourth most common carcinoma in women in the world. The JAK/STAT3 signaling pathways crucially regulate cell growth and apoptosis. It is a significant target signaling pathway for the development of novel antitumor medicine. This study intended to explore whether lycorine could prevent HT-3 proliferation and induce apoptosis by targeting the JAK/STAT3 signaling cascade. The HT-3 cells were treated with various lycorine dosages and we analyzed cell growth, lipid peroxidation, antioxidants, mitochondrial membrane potential (ΔΨm), DNA damage, apoptosis markers by different in vitro methodologies. Our results revealed that lycorine substantially reserved cell growth via decreased antioxidants, augmented reactive oxygen species (ROS) generation which leads to loss of ΔΨm, increased nuclear crumbling and chromatin condensation, thus resulting in representative increased apoptotic cell death. Furthermore, we analyzed that the molecular mechanical action of lycorine considerably repressed JAK1/STAT3 transactional activation and decrease its downstream molecules Bcl-2, and enhances the expressional activity of Bax, cytochrome c, caspase 3 and 9 in HT-3 cells. Finally, the fact that N-acetylcysteine inhibits lycorine-induced ROS-mediated apoptosis was confirmed in HT-3 cells. Thus, the results indicate that lycorine efficiently enhances apoptosis and inhibits HT-3 cell proliferation. These outcomes collectively proposed that lycorine could be a beneficial chemotherapeutic agent for treating and managing human cervical carcinoma.

中文翻译：

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石蒜碱通过调节 HT-3 细胞中的 JAK/STAT3 信号通路抑制细胞增殖和诱导氧化应激介导的细胞凋亡

人类宫颈癌是世界上女性第四常见的癌症。JAK/STAT3 信号通路至关重要地调节细胞生长和凋亡。它是开发新型抗肿瘤药物的重要靶信号通路。本研究旨在探讨石蒜碱是否可以通过靶向 JAK/STAT3 信号级联来阻止 HT-3 增殖和诱导细胞凋亡。HT-3 细胞用不同剂量的石蒜碱处理，我们通过不同的体外方法分析了细胞生长、脂质过氧化、抗氧化剂、线粒体膜电位 (ΔΨm)、DNA 损伤、细胞凋亡标志物。我们的研究结果表明，lycorine 通过减少抗氧化剂、增加活性氧 (ROS) 的产生从而导致 ΔΨm 的损失显着保留了细胞生长，增加核破碎和染色质凝聚，从而导致代表性增加的凋亡细胞死亡。此外，我们分析了石蒜碱的分子机械作用显着抑制 JAK1/STAT3 交易激活并减少其下游分子 Bcl-2，并增强 Bax、细胞色素的表达活性。c，HT-3细胞中的半胱天冬酶3和9。最后，在 HT-3 细胞中证实了N-乙酰半胱氨酸抑制石蒜碱诱导的 ROS 介导的细胞凋亡的事实。因此，结果表明石蒜碱有效地增强细胞凋亡并抑制HT-3细胞增殖。这些结果共同提出，lycorine 可能是治疗和管理人类宫颈癌的有益化学治疗剂。