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丹参酮 IIA 通过降低 LC3-II、Erb-B2 和 NF-κBp65 抑制人乳腺癌 MDA-MB-231 细胞。

Tanshinone IIA inhibits human breast cancer MDA-MB-231 cells by decreasing LC3-II, Erb-B2 and NF-κBp65.

机构信息

Department of Surgery, Comprehensive Breast Cancer Center, Laboratory of Integrative Medicine Cancer Research, Changhua Christian Hospital, Changhua 500-06, Taiwan, ROC.

出版信息

Mol Med Rep. 2012 Apr;5(4):1019-22. doi: 10.3892/mmr.2012.756. Epub 2012 Jan 13.

Abstract

The ability of tanshinone IIA (Tan-IIA) to inhibit the proliferation of human breast cancer cell lines in vitro and in vivo is well documented. However, the molecular mechanisms have not been fully elucidated. In the present study, MDA-MB-231 cells were treated with different concentrations of Tan-IIA for 48 h, followed by protein extraction for western blotting. For an in vivo study, MDA-MB-231 cells were implanted directly into female SCID mice which were divided randomly into three groups to be treated with vehicle, Tan-IIA (20 mg/kg) and Tan-IIA (60 mg/kg) every other day orally, with treatment starting 4 weeks after inoculation with the MDA-MB-231 cells. The results showed that Tan-IIA inhibited the proliferation of MDA-MB-231 cells and decreased the protein expression of LC3-II and Erb-B2 in vitro. Treatment with Tan-IIA (20 or 60 mg/kg) for 90 days resulted in a reduction in tumor size and weight compared to the control group. The protein expression of NF-κBp65 was reduced, while caspase-3 was up-regulated compared to the control group. These findings indicate that Tan-IIA inhibits tumor growth in a MDA-MB-231 xenograft animal model. One of the molecular mechanisms may be through a decrease in NF-κBp65 and an increase in caspase-3 expression.

摘要

丹参酮 IIA(Tan-IIA)抑制人乳腺癌细胞系在体外和体内增殖的能力已有充分的文献记载。然而,其分子机制尚未完全阐明。在本研究中,用不同浓度的 Tan-IIA 处理 MDA-MB-231 细胞 48 小时,然后提取蛋白进行 Western blot 分析。在体内研究中,将 MDA-MB-231 细胞直接植入雌性 SCID 小鼠中,随机分为三组,分别给予 vehicle、Tan-IIA(20mg/kg)和 Tan-IIA(60mg/kg),每天口服一次,从接种 MDA-MB-231 细胞后 4 周开始治疗。结果表明,Tan-IIA 抑制 MDA-MB-231 细胞的增殖,并降低 LC3-II 和 Erb-B2 的蛋白表达。与对照组相比,Tan-IIA(20 或 60mg/kg)治疗 90 天可降低肿瘤大小和重量。与对照组相比,NF-κBp65 的蛋白表达降低,而 caspase-3 的表达上调。这些发现表明 Tan-IIA 抑制 MDA-MB-231 异种移植动物模型中的肿瘤生长。其分子机制之一可能是通过降低 NF-κBp65 和增加 caspase-3 的表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7400/3493065/79546a1114ed/MMR-05-04-1019-g01.jpg

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