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臭椿酮抑制膀胱癌肿瘤生长、细胞增殖、上皮-间质转化以及Janus激酶/信号转导子和转录激活子3信号通路的激活。

Ailanthone inhibits bladder cancer tumor and cell proliferation, epithelial-mesenchymal transition, and activation of the Janus kinase/signal transducer and activator of transcription 3 signaling pathway.

作者信息

Li Jian, Lv You, Xue Sheng, Li Wenyong, Zhang Xiaole

机构信息

Department of Urology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui Province, China.

出版信息

Cytojournal. 2025 Feb 12;22:16. doi: 10.25259/Cytojournal_166_2024. eCollection 2025.

DOI:10.25259/Cytojournal_166_2024
PMID:40134568
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11932951/
Abstract

OBJECTIVE

Ailanthone (AIL), a medicinal component with antitumor properties, was distilled from . The aim of this work was to probe the cancer-fighting effect of AIL on bladder cancer (BC) cells and the molecular basis of this effect.

MATERIAL AND METHODS

We developed a subcutaneous BC mouse model and then administered AIL treatment. The effects of AIL on tumor tissue integrity and apoptosis were analyzed using hematoxylin and eosin (H&E) staining and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining methods. Furthermore, we investigated the effect of AIL on the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway and associated proteins through quantitative reverse transcription polymerase chain reaction and Western blot analysis. Various concentrations of AIL were applied to BC cells, and its effects on cell survival, motility, and apoptosis were detected through cell counting kit-8 assay, Transwell assay, and flow cytometry. In addition, we examined the influence of AIL on apoptosis-related proteins and epithelialmesenchymal transition (EMT)-related proteins in BC cells through Western blot analysis.

RESULTS

AIL significantly suppressed the growth and migration of 5637 and T24 cells while promoting apoptosis ( < 0.05, < 0.01, and < 0.001). In addition, AIL increased the levels of cell death-associated proteins ( < 0.05, < 0.01, and < 0.001) and reversed EMT in BC cells. , AIL treatment reduced tumor growth and lowered the transcriptional levels of interleukin (IL)-6, IL-10, and IL-23, which are activation factors in the JAK/STAT3 signaling pathway. It also decreased the phosphorylation levels of JAK1, JAK2, and STAT3 in tumor tissues ( < 0.05 and < 0.01).

CONCLUSION

AIL exhibits multiple anticancer effects, such as BC cell growth suppression, apoptosis enhancement, reversion of EMT reversion, tumor growth, and JAK/STAT3 pathway activation suppression.

摘要

目的

从 中提取出具有抗肿瘤特性的药用成分樗酮(AIL)。本研究旨在探究 AIL 对膀胱癌细胞(BC)的抗癌作用及其作用的分子基础。

材料与方法

我们构建了皮下 BC 小鼠模型,随后进行 AIL 治疗。采用苏木精-伊红(H&E)染色和末端脱氧核苷酸转移酶 dUTP 缺口末端标记(TUNEL)染色方法分析 AIL 对肿瘤组织完整性和细胞凋亡的影响。此外,我们通过定量逆转录聚合酶链反应和蛋白质免疫印迹分析研究 AIL 对 Janus 激酶/信号转导子和转录激活子 3(JAK/STAT3)通路及相关蛋白的影响。将不同浓度的 AIL 应用于 BC 细胞,通过细胞计数试剂盒-8 检测法、Transwell 检测法和流式细胞术检测其对细胞存活、迁移和凋亡的影响。此外,我们通过蛋白质免疫印迹分析检测 AIL 对 BC 细胞中凋亡相关蛋白和上皮-间质转化(EMT)相关蛋白的影响。

结果

AIL 显著抑制 5637 和 T24 细胞的生长和迁移,同时促进细胞凋亡(<0.05,<0.01,<0.001)。此外,AIL 增加了细胞死亡相关蛋白的水平(<0.05,<0.01,<0.001),并逆转了 BC 细胞中的 EMT。 ,AIL 治疗可降低肿瘤生长,并降低 JAK/STAT3 信号通路激活因子白细胞介素(IL)-6、IL-10 和 IL-23 的转录水平。它还降低了肿瘤组织中 JAK1、JAK2 和 STAT3 的磷酸化水平(<0.05 和<0.01)。

结论

AIL 具有多种抗癌作用,如抑制 BC 细胞生长、增强细胞凋亡、逆转 EMT、抑制肿瘤生长以及抑制 JAK/STAT3 通路激活。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a46d/11932951/a807b839168d/Cytojournal-22-16-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a46d/11932951/30459f1be098/Cytojournal-22-16-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a46d/11932951/1caf27c65efe/Cytojournal-22-16-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a46d/11932951/3b79382e0a6b/Cytojournal-22-16-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a46d/11932951/01bf06f800c1/Cytojournal-22-16-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a46d/11932951/d4140e4c38f0/Cytojournal-22-16-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a46d/11932951/a807b839168d/Cytojournal-22-16-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a46d/11932951/30459f1be098/Cytojournal-22-16-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a46d/11932951/1caf27c65efe/Cytojournal-22-16-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a46d/11932951/3b79382e0a6b/Cytojournal-22-16-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a46d/11932951/01bf06f800c1/Cytojournal-22-16-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a46d/11932951/d4140e4c38f0/Cytojournal-22-16-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a46d/11932951/a807b839168d/Cytojournal-22-16-g006.jpg

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