Zhong Lili, Li Jiaxin, Zhong Jianfeng, Zhang Yifan, Qi Hang, Yu Huimei, Li Xin
Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, Jilin, China.
Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, China.
J Cell Mol Med. 2025 Aug;29(15):e70728. doi: 10.1111/jcmm.70728.
Cervical cancer ranks as the second most prevalent cancer among women worldwide, and the primary treatment for advanced cases involves cisplatin-based chemotherapy. However, the duration of cisplatin treatment is typically short, with a median survival rate of approximately 1 year. This highlights the urgent need to enhance our understanding of cisplatin's mechanism of action in cervical cancer treatment. Our findings demonstrate that p53 induces the nuclear translocation of IFI16, leading to activation of the NF-κB signalling pathway. This activation plays a crucial role in protecting cervical cancer cells against cisplatin-induced apoptosis. The activation of NF-κB is independent of STING, which is a downstream molecule of IFI16. STING signalling activation by cisplatin may not be associated with cisplatin-induced apoptosis. To further validate this tumour-promoting effect of IFI16 during cisplatin therapy, we established a subcutaneous implantation tumour model using mouse cervical cancer (U14) cells and conducted additional in vitro experiments. We examined the role and mechanism of IFI16 in cisplatin treatment of cervical cancer. The role of IFI16 in cervical cancer progression deserves further study. Targeted inhibition of IFI16 may be a new way to increase cisplatin sensitivity of cervical cancer cells.
宫颈癌是全球女性中第二大常见癌症，晚期病例的主要治疗方法是基于顺铂的化疗。然而，顺铂治疗的持续时间通常较短，中位生存率约为1年。这凸显了迫切需要加强我们对顺铂在宫颈癌治疗中作用机制的理解。我们的研究结果表明，p53诱导IFI16的核转位，导致NF-κB信号通路激活。这种激活在保护宫颈癌细胞免受顺铂诱导的凋亡中起关键作用。NF-κB的激活独立于IFI16的下游分子STING。顺铂诱导的STING信号激活可能与顺铂诱导的凋亡无关。为了进一步验证IFI16在顺铂治疗期间的这种促肿瘤作用，我们使用小鼠宫颈癌（U14）细胞建立了皮下植入肿瘤模型，并进行了额外的体外实验。我们研究了IFI16在顺铂治疗宫颈癌中的作用和机制。IFI16在宫颈癌进展中的作用值得进一步研究。靶向抑制IFI16可能是提高宫颈癌细胞对顺铂敏感性的一种新方法。
