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| Renieramycin T通过Nrf2-STAT3信号通路抑制结直肠癌细胞的迁移和侵袭 |
| Renieramycin T inhibits CRC cell migration and invasion via Nrf2-STAT3 dependent manner |
| 投稿时间：2025-01-22 修订日期：2025-04-08 |
| DOI： |
| 中文关键词: Renieramycin T；结直肠癌；肿瘤迁移与侵袭; p-STAT3; Nrf2 |
| 英文关键词: Renieramycin T; Colorectal cancer; cell migration and invasion; p-STAT3; Nrf2 |
| 基金项目:济宁医学院贺林院士新医学临床转化工作站科研基金 |
| 作者 | 单位 | 邮编 | | 张长悦 | 滨州医学院药学院 | 264003 | | 梁敬 | 济宁医学院医学影像与检验学院 | | | 陈瑞蛟* | 济宁医学院医学影像与检验学院 | 272067 |
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| 中文摘要: |
| 目的 已有研究表明Renieramycin T（RT）可抑制多种肿瘤的发生发展，RT通过靶向降解Mcl-1而介导肺癌细胞死亡，通过调控Nrf2和STAT3信号通路抑制黑色素瘤B16F10细胞的转移和侵袭等。然而，RT对结直肠癌的作用并不清楚。本研究旨在探究RT抗结直肠癌活性，并初步揭示其发挥抑制作用的分子机制。 方法 利用THP-1细胞的上清液与HCT116细胞进行条件培养，模拟肿瘤微环境。THP-1细胞的具体处理条件为：THP-1细胞接种于6孔板（2×105cells/孔），PMA（80ng/mL）处理24h，用PBS洗涤，随后换无PMA培养基静置24h，IL-4+IL-13（各20ng/mL）刺激48h，PBS洗涤，换无血清培养基培养24h，收集上清液离心过滤，最后与HCT116培养基1:1混合。用RT处理HCT116细胞，CCK-8实验检测细胞活性变化。细胞划痕实验检测细胞迁移能力变化，Transwell实验检测细胞侵袭能力变化，Western blotting实验探索其分子机制。实验分组为空白对照组、THP-1与HCT116细胞的共培养（CM）、CM+RT 20nM、CM+RT 80nM。结果RT能以浓度依赖性的方式抑制肿瘤微环境下的HCT116细胞的迁移和侵袭。此外，Western Blot结果显示，RT可抑制磷酸化STAT3和Nrf2的表达。结论 RT可通过Nrf2-STAT3信号抑制结直肠癌细胞转移，可能成为一种治疗转移性结肠癌的新型药物。 |
| 英文摘要: |
| Objective It has been shown that Renieramycin T (RT) inhibits the progression of various tumors. For example, RT mediates lung cancer cell death by targeting the degradation of Mcl-1; inhibits metastasis and invasion of melanoma B16F10 cells by regulating the Nrf2 and STAT3 signal pathways. However, the role of RT on colorectal cancer progression is not clear. The aim of this study was to investigate the anti-colorectal cancer activity of RT and to reveal the molecular mechanism by which it exerts its inhibitory effect. Methods An inflammation-associated model was established by co-culture of supernatants of THP-1 cells with HCT116 cells. The specific treatment conditions of THP-1 cells were as follows: THP-1 cells were inoculated in 6-well plates (2×105cells/well), treated with PMA (80 ng/mL) for 24h, washed with PBS, followed by switching to PMA-free medium for 24h of resting, and stimulated with IL-4 + IL-13 (20 ng/mL each) for 48h, washed with PBS, and switched to serum-free medium for 24h of incubation. The supernatant was collected, centrifuged and filtered, and finally mixed 1:1 with HCT116 medium. The HCT116 cells were then treated with RT. CCK-8 assay was used to detect the changes in cell activity, cell migration was detected by wound healing assay, cell invasion was detected by Trans-well assay, and the molecular mechanism was verified by western blotting. The experimental groups were blank control group, co-culture (CM) of THP-1 and HCT116 cells, CM+RT20nM, CM+RT80nM. Results The results showed that RT inhibited the migration and invasion of HCT116 cells induced by THP-1 cell supernatant in a concentration-dependent manner. Moreover, western blot results showed that RT inhibited STAT3 phosphorylation and Nrf2 expression. Conclusion RT inhibits CRC cell metastasis through Nrf2-STAT3 signaling. This may be a novel drug for the treatment of metastatic colon cancer. |
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