Yu Lu, Li Wei
Department of Obstetrics and Gynaecology, People's Hospital of China Three Gorges University Yichang 443000, Hubei, China.
Int J Clin Exp Pathol. 2022 Jan 15;15(1):11-19. eCollection 2022.
Notch1 signaling pathway is an evolutionarily conserved and crucial regulator to determine cell fate and differentiation. Notch1 is often over expressed in several cancers, which plays an essential for cancer cell proliferation, survival, invasion and metastasis. The oncogenic function of Notch1 signaling in cervical cancer progression is not well-characterized. In the present study, we showed that Notch1 is significantly enhanced in cervical cancer tissues. Similarly, the relative mRNA and expression of Notch1 protein are significantly upregulated in cervical cancer cell lines such as HeLa and SiHa. Further, we have performed RNAi for depletion to determine its specific role in cervical cancer progression. Flow cytometry analysis revealed that depletion leads to activation of apoptotic cell death in cervical cancer. Further, the depleted cells showed increased sensitivity towards DNA-targeting drugs and therefore cell viability was reduced efficiently. Altogether, our findings suggest that Notch1 overexpression in cervical cancer cells was involved in tumorigenesis and apoptosis resistance of cervical cancer.
Notch1信号通路是一种在进化上保守且对决定细胞命运和分化至关重要的调节因子。Notch1在多种癌症中常过度表达，对癌细胞的增殖、存活、侵袭和转移起着至关重要的作用。Notch1信号在宫颈癌进展中的致癌功能尚未得到充分表征。在本研究中，我们发现Notch1在宫颈癌组织中显著增强。同样，在HeLa和SiHa等宫颈癌细胞系中，Notch1蛋白的相对mRNA和表达也显著上调。此外，我们进行了RNA干扰以确定其在宫颈癌进展中的具体作用。流式细胞术分析显示，Notch1缺失导致宫颈癌细胞凋亡死亡的激活。此外，Notch1缺失的细胞对靶向DNA的药物表现出更高的敏感性，因此细胞活力有效降低。总之，我们的研究结果表明，宫颈癌细胞中Notch1的过表达参与了宫颈癌的肿瘤发生和凋亡抵抗。
