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通过JAK-STAT通路抑制肝癌细胞增殖并诱导其凋亡:一项临床前研究

Inhibits Proliferation and Induces Apoptosis of Hepatocellular Carcinoma via JAK-STAT Pathway: A Preclinical Study.

作者信息

Lin Lili, Chen Qi

机构信息

Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Science, Fujian Normal University Qishan Campus, College Town, Fuzhou 350117, China.

出版信息

Biology (Basel). 2024 Jul 16;13(7):528. doi: 10.3390/biology13070528.

Abstract

Liver cancer is a significant global health concern, prompting the search for innovative therapeutic solutions. (), a natural derivative of Brucea javanica, has emerged as a promising candidate for cancer treatment; however, its efficacy and underlying mechanisms in liver cancer remain incompletely understood. In this study, we conducted a comprehensive evaluation of s effects on liver cancer cells using a range of in vitro assays and an orthotopic liver cancer mouse model. Our findings reveal that exerts dose-dependent cytotoxic effects on liver cancer cells, significantly inhibiting proliferation, migration, and invasion at concentrations ≥ 0.1 μM. Furthermore, induces apoptosis, as evidenced by increased apoptotic cell populations and apoptosome formation. In vivo studies confirm that inhibits tumor growth and reduces liver damage in mouse models. Mechanistically, targets the TNF-α/STAT3 pathway, inhibiting STAT3 and JAK2 phosphorylation, thereby activating apoptotic pathways and suppressing tumor cell growth. These results suggest that has promising anticancer activity and potential utility in liver cancer therapy.

摘要

肝癌是一个重大的全球健康问题,促使人们寻找创新的治疗方案。鸦胆子素(一种鸦胆子的天然衍生物)已成为一种有前景的癌症治疗候选药物;然而,其在肝癌中的疗效和潜在机制仍不完全清楚。在本研究中,我们使用一系列体外实验和原位肝癌小鼠模型对鸦胆子素对肝癌细胞的作用进行了全面评估。我们的研究结果表明,鸦胆子素对肝癌细胞具有剂量依赖性的细胞毒性作用,在浓度≥0.1μM时显著抑制增殖、迁移和侵袭。此外,鸦胆子素诱导细胞凋亡,凋亡细胞群体增加和凋亡小体形成证明了这一点。体内研究证实,鸦胆子素在小鼠模型中抑制肿瘤生长并减少肝损伤。从机制上讲,鸦胆子素靶向TNF-α/STAT3途径,抑制STAT3和JAK2磷酸化,从而激活凋亡途径并抑制肿瘤细胞生长。这些结果表明,鸦胆子素在肝癌治疗中具有有前景的抗癌活性和潜在用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2996/11274273/4c8b9195e56f/biology-13-00528-g001.jpg

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