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绿原酸通过 NF-κB 信号通路诱导乳腺癌细胞凋亡、抑制转移并增强抗肿瘤免疫。

Chlorogenic acid induces apoptosis, inhibits metastasis and improves antitumor immunity in breast cancer via the NF‑κB signaling pathway.

机构信息

West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, P.R. China.

School of Medical and Life Sciences/Reproductive and Women‑Children Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, P.R. China.

出版信息

Oncol Rep. 2021 Feb;45(2):717-727. doi: 10.3892/or.2020.7891. Epub 2020 Dec 9.

Abstract

Breast cancer which is the most common type of diagnosed cancer among women worldwide possesses metastatic potential, multi‑drug resistance, and high mortality. The NF‑κB signaling pathway has been revealed to be abnormally activated in breast cancer cells and closely associated with high metastasis and poor prognosis. In the present study, it was reported that chlorogenic acid (CGA), a potent NF‑κB inhibitor derived from coffee, exerted antitumor activity in breast cancer. MTT and colony formation assays were conducted and it was revealed that CGA inhibited viability and proliferation in breast cancer cells. Additionally, CGA significantly induced apoptosis and suppressed migration and invasion in breast cancer cells. Notably, immunofluorescence analysis confirmed that CGA could efficiently suppress nuclear transcription of NF‑κB p65. In addition, results of western blotting demonstrated that CGA markedly impaired the NF‑κB and EMT signaling pathways. The antitumor effect of CGA was evaluated in a subcutaneous tumor mouse model of 4T1 cells, and the results revealed that CGA markedly retarded tumor growth and prolonged the survival rate of tumor‑bearing mice. Notably, CGA inhibited pulmonary metastasis of 4T1 cells by enhancing the proportion of CD4+ and CD8+ T cells in spleens of mice, which indicated an improvement of antitumor immunity. In conclusion, the present present study demonstrated that CGA improved antitumor immunity, exerting antitumor and anti‑metastatic effects by impairing the NF‑κB/EMT signaling pathway, suggesting that CGA may serve as a potential candidate for therapy of breast cancer.

摘要

乳腺癌是全球女性中最常见的诊断癌症类型,具有转移潜能、多药耐药性和高死亡率。已经发现 NF-κB 信号通路在乳腺癌细胞中异常激活,并与高转移和不良预后密切相关。本研究报道了咖啡中提取的强效 NF-κB 抑制剂绿原酸(CGA)在乳腺癌中具有抗肿瘤活性。进行了 MTT 和集落形成测定,结果表明 CGA 抑制乳腺癌细胞的活力和增殖。此外,CGA 显著诱导乳腺癌细胞凋亡并抑制迁移和侵袭。值得注意的是,免疫荧光分析证实 CGA 能够有效地抑制 NF-κB p65 的核转录。此外,Western blot 结果表明 CGA 显著削弱了 NF-κB 和 EMT 信号通路。在 4T1 细胞的皮下肿瘤小鼠模型中评估了 CGA 的抗肿瘤作用,结果表明 CGA 显著延缓了肿瘤生长并延长了荷瘤小鼠的生存率。值得注意的是,CGA 通过增强小鼠脾脏中 CD4+和 CD8+T 细胞的比例来抑制 4T1 细胞的肺转移,这表明抗肿瘤免疫得到了改善。总之,本研究表明 CGA 通过抑制 NF-κB/EMT 信号通路改善了抗肿瘤免疫,发挥了抗肿瘤和抗转移作用,提示 CGA 可能成为治疗乳腺癌的潜在候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8343/7757108/cedef0f1d2a1/OR-45-02-0717-g00.jpg

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