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薯蓣皂苷通过靶向BMI1-Noxa轴诱导口腔鳞状细胞癌细胞凋亡。

Targeting the BMI1-Noxa axis by Dioscin induces apoptosis in oral squamous cell carcinoma cells.

作者信息

Fang Jinglin, Wang Ruirui, Li Xiaoying, Wang XiaoCong, Gong Lingling, Lou An, Lu Jie, Zhang Xiaoyue, Zhao Qin, Yu Xinfang, Zhou Qiling, Li Ming

机构信息

School of Stomatology, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China.

Changsha Stomatological Hospital, Changsha, Hunan 410004, China.

出版信息

J Cancer. 2025 Jan 1;16(1):110-121. doi: 10.7150/jca.100631. eCollection 2025.

Abstract

Dioscin is a natural plant-derived steroidal saponin that exerts antitumor effects in multiple cancers. It is widely involved in multiple apoptotic pathways and exerts its anti-tumor effects. In this study, we discovered that Dioscin treatment increased the expression of Noxa, thereby inducing the apoptosis of OSCC cells. Previous reports indicate that dysfunction of the BMI1-Noxa axis is frequently observed in multiple cancers. Our study revealed that Dioscin upregulates Noxa by impairing the protein expression of BMI1 in OSCC cells. Dioscin promotes the ubiquitination of BMI1 and facilitates its degradation, leading to upregulation of Noxa expression at the mRNA level and activation of apoptosis. Additionally, Dioscin exhibited potent tumor suppression in xenograft tumor models. In conclusion, our research provides new insights and strategies for inhibiting OSCC cells by investigating the ant-tumor mechanism of the natural compound Dioscin.

摘要

薯蓣皂苷是一种天然植物来源的甾体皂苷,在多种癌症中发挥抗肿瘤作用。它广泛参与多种凋亡途径并发挥其抗肿瘤作用。在本研究中,我们发现薯蓣皂苷处理可增加Noxa的表达,从而诱导口腔鳞状细胞癌(OSCC)细胞凋亡。先前的报道表明,BMI1-Noxa轴功能障碍在多种癌症中经常出现。我们的研究表明,薯蓣皂苷通过损害OSCC细胞中BMI1的蛋白表达来上调Noxa。薯蓣皂苷促进BMI1的泛素化并促进其降解,导致Noxa表达在mRNA水平上调并激活凋亡。此外,薯蓣皂苷在异种移植肿瘤模型中表现出强大的肿瘤抑制作用。总之,我们的研究通过研究天然化合物薯蓣皂苷的抗肿瘤机制,为抑制OSCC细胞提供了新的见解和策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c19c/11660131/0dd8257cda86/jcav16p0110g001.jpg

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