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栀子苷通过抑制 PI3K/AKT/mTOR 通路促进神经母细胞瘤细胞的凋亡和自噬。

Genipin promotes the apoptosis and autophagy of neuroblastoma cells by suppressing the PI3K/AKT/mTOR pathway.

机构信息

Department of Paediatrics, Affiliated Hospital of North Sichuan Medical College, No. 1 Maoyuan South Road, Shunqing District, Nanchong, 637000, Sichuan, China.

Science and Technology Innovation Centre, North Sichuan Medical College, Shunqing District, Nanchong, 637000, Sichuan, China.

出版信息

Sci Rep. 2024 Aug 30;14(1):20231. doi: 10.1038/s41598-024-71123-w.

Abstract

This study investigated the underlying function and mechanism of genipin in neuroblastoma (NB). Using flow cytometry analysis and cytotoxicity tests, in vitro studies were conducted to assess the effects of genipin on the SK-N-SH cell line. The mechanism of action of genipin was explored through immunofluorescence staining, Western blotting, and caspase-3 activity assays. In addition, we also created a xenograft tumour model to investigate the effects of genipin in vivo. This research confirmed that genipin suppressed cell viability, induced apoptosis, and promoted autophagy, processes that are likely linked to the inhibition of the PI3K/AKT/mTOR signalling pathway. Autophagy inhibition increases the sensitivity of SK-N-SH cells to genipin. Furthermore, combination treatment with a PI3K inhibitor enhanced the therapeutic efficacy of genipin. These results highlight the potential of genipin as a candidate drug for the treatment of NB.

摘要

本研究探讨了京尼平在神经母细胞瘤(NB)中的潜在作用和机制。通过流式细胞术分析和细胞毒性试验,进行了体外研究,以评估京尼平对 SK-N-SH 细胞系的影响。通过免疫荧光染色、Western blot 和 caspase-3 活性测定,探讨了京尼平的作用机制。此外,我们还创建了异种移植肿瘤模型,以研究京尼平在体内的作用。这项研究证实,京尼平抑制细胞活力,诱导细胞凋亡,并促进自噬,这些过程可能与抑制 PI3K/AKT/mTOR 信号通路有关。自噬抑制增加了 SK-N-SH 细胞对京尼平的敏感性。此外,与 PI3K 抑制剂联合治疗增强了京尼平的治疗效果。这些结果突出了京尼平作为治疗 NB 的候选药物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77e0/11364629/49f613254865/41598_2024_71123_Fig1_HTML.jpg

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