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舒芬太尼通过介导 NF-κB 通路抑制乳腺癌的转移和免疫反应。

Sufentanil inhibits the metastasis and immune response of breast cancer via mediating the NF-κB pathway.

机构信息

Department of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin, China.

Department of Gastroenterology and Hepatology, The Second Hospital of Harbin, Harbin, China.

出版信息

Immunopharmacol Immunotoxicol. 2023 Dec;45(6):663-671. doi: 10.1080/08923973.2023.2228476. Epub 2023 Jul 6.

DOI:10.1080/08923973.2023.2228476
PMID:37358084
Abstract

OBJECTIVE

Breast cancer (BC) causes cancer-related death in women. Sufentanil is used for cancer pain and postoperative analgesia. This study aimed to explore the role of sufentanil in BC.

METHODS

BC cells were treated with sufentanil, and cell viability was evaluated using the cell counting kit-8 (CCK-8) assay. Biological behaviors were analyzed using EDU assay, flow cytometry, transwell assay, western blotting, and ELISA. The levels of NF-κB pathway-related factors were examined using western blotting. A xenograft tumor model was established to assess the effects of sufentanil on tumor growth .

RESULTS

Sufentanil at the concentration of 20, 40, 80, and 160 nM suppressed cell viability (IC50 = 39.84 in MDA-MB-231 cells, and IC50 = 47.46 in BT549 cells). Sufentanil inhibited the proliferation, invasion, epithelial-mesenchymal transition (EMT), and inflammation, but induced apoptosis of BC cells. Mechanically, sufentanil suppressed the activation of the NF-κB pathway. Rescue experiments showed that RANKL (NF-κB receptor agonist) abrogated the effects induced by sufentanil. Moreover, sufentanil inhibited tumor growth, inflammatory response, but promoted apoptosis the NF-κB pathway .

CONCLUSIONS

Sufentanil decelerated the progression of BC by regulating the NF-κB pathway, suggesting sufentanil may be used in BC therapy.

摘要

目的

乳腺癌(BC)导致女性癌症相关死亡。舒芬太尼用于治疗癌症疼痛和术后镇痛。本研究旨在探讨舒芬太尼在 BC 中的作用。

方法

用舒芬太尼处理 BC 细胞,用细胞计数试剂盒-8(CCK-8)检测细胞活力。通过 EDU 检测、流式细胞术、Transwell 检测、Western blot 和 ELISA 分析生物学行为。用 Western blot 检测 NF-κB 通路相关因子的水平。建立异种移植肿瘤模型,评估舒芬太尼对肿瘤生长的影响。

结果

浓度为 20、40、80 和 160 nM 的舒芬太尼抑制细胞活力(IC50 在 MDA-MB-231 细胞中为 39.84,在 BT549 细胞中为 47.46)。舒芬太尼抑制 BC 细胞的增殖、侵袭、上皮-间充质转化(EMT)和炎症,但诱导细胞凋亡。机制上,舒芬太尼抑制 NF-κB 通路的激活。挽救实验表明,RANKL(NF-κB 受体激动剂)消除了舒芬太尼诱导的作用。此外,舒芬太尼抑制肿瘤生长、炎症反应,但促进 NF-κB 通路介导的细胞凋亡。

结论

舒芬太尼通过调节 NF-κB 通路减缓 BC 的进展,表明舒芬太尼可能用于 BC 的治疗。

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