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人参皂苷 Rg3 通过抑制 NF-κB 信号通路和调节三阴性乳腺癌中 Bax/Bcl-2 的表达来增强紫杉醇的细胞毒性。

Ginsenoside Rg3 promotes cytotoxicity of Paclitaxel through inhibiting NF-κB signaling and regulating Bax/Bcl-2 expression on triple-negative breast cancer.

机构信息

Department of Radiotherapy, Yinzhou People's Hospital, Ningbo, Zhejiang 315040, PR China.

Department of Oncology, Zhejiang Hospital, Hangzhou, Zhejiang 310013, PR China.

出版信息

Biomed Pharmacother. 2017 May;89:227-232. doi: 10.1016/j.biopha.2017.02.038. Epub 2017 Feb 20.

Abstract

Taxane-based chemotherapy regimen is the most effective therapeutic strategy for triple-negative breast cancer (TNBC) which is an aggressive subtype of breast cancer with high rate of recurrence and distant metastasis. Ginsenoside Rg3 is isolated from Panax ginseng with anti-cancer activity against carcinomas. We aim to evaluate the chemosensitizing effects of Ginsenoside Rg3 on TNBC cells and xenograft and explore the underlying mechanism. Human triple-negative breast cancer lines MDA-MB-231, MDA-MB-453 and BT-549 were used. Cell viability and survival was detected by MTT assay and colony formation assay. Apoptosis was detected by Annexin V/PI assay and TUNEL. Enzyme-linked immunosorbent assay was performed to determine NF-κB activation. The NF-κB p65, Bcl 2, Bax and Caspase-3 protein expression were detected using Western blot analysis. The results showed that Ginsenoside Rg3 promotes cytotoxicity and apoptosis of Paclitaxel on TNBC cell lines and xenograft. Ginsenoside Rg3 combined Paclitaxel inhibited NF-κB activation, decreased NF-κB p65 and Bcl-2 protein expressions, increased Bax and Caspase-3 protein expressions. The ratio of Bax/Bcl-2 was significantly enhanced by the Ginsenoside Rg3 to Paclitaxel. Ginsenoside Rg3 promotes cytotoxicity and apoptosis of Paclitaxel by inhibiting NF-κB signaling and modulating Bax/Bcl-2 expression on TNBC. Ginsenoside Rg3 should be regarded as a good chemosensitizing agent for TNBC treatment.

摘要

基于紫杉烷的化疗方案是三阴性乳腺癌(TNBC)的最有效治疗策略,TNBC 是一种侵袭性乳腺癌亚型,复发率和远处转移率高。人参皂苷 Rg3 是从人参中分离出来的,具有抗癌活性,可对抗癌。我们旨在评估人参皂苷 Rg3 对 TNBC 细胞和异种移植的化疗增敏作用,并探讨其潜在机制。使用人三阴性乳腺癌细胞系 MDA-MB-231、MDA-MB-453 和 BT-549。通过 MTT 检测和集落形成检测来检测细胞活力和存活。通过 Annexin V/PI 检测和 TUNEL 检测来检测细胞凋亡。通过酶联免疫吸附试验来检测 NF-κB 激活。通过 Western blot 分析检测 NF-κB p65、Bcl 2、Bax 和 Caspase-3 蛋白表达。结果表明,人参皂苷 Rg3 促进紫杉醇对 TNBC 细胞系和异种移植的细胞毒性和细胞凋亡。人参皂苷 Rg3 联合紫杉醇抑制 NF-κB 激活,降低 NF-κB p65 和 Bcl-2 蛋白表达,增加 Bax 和 Caspase-3 蛋白表达。人参皂苷 Rg3 与紫杉醇联合使用显著增强了 Bax/Bcl-2 的比值。人参皂苷 Rg3 通过抑制 NF-κB 信号通路和调节 Bax/Bcl-2 表达来促进紫杉醇对 TNBC 的细胞毒性和细胞凋亡。人参皂苷 Rg3 应被视为治疗 TNBC 的一种良好化疗增敏剂。

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