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穿心莲内酯通过抑制TLR4/NF-κB信号通路抑制多发性骨髓瘤细胞。

Andrographolide inhibits multiple myeloma cells by inhibiting the TLR4/NF-κB signaling pathway.

作者信息

Gao Hui, Wang Jianrong

机构信息

Department of Hematology, Dongying People's Hospital of Shandong, Dongying, Shandong 257091, P.R. China.

Department of Obstetrics, Dongying People's Hospital of Shandong, Dongying, Shandong 257091, P.R. China.

出版信息

Mol Med Rep. 2016 Feb;13(2):1827-32. doi: 10.3892/mmr.2015.4703. Epub 2015 Dec 22.

Abstract

Andrographolide is an active component from the extract of Andrographis paniculata [(Burm.f) Nees], a medicinal plant from the Acanthaceae family. Pharmacological studies have revealed that andrographolide possesses anti-bacterial, anti-inflammatory, anti-viral, immune regulatory and hepatoprotective properties, and is efficacious in the treatment of cardiovascular diseases, while exhibiting low toxicity and low cost. The present study aimed to determine the inhibitory effects of andrographolide on the growth of multiple myeloma (MM) cells and its possible impact on the Toll-like receptor (TLR)4/nuclear factor (NF)-κB signaling pathway. Cell proliferation was detected using an MTT assay, cellular apoptosis was measured using flow cytometry, and caspase-9/3 activation were assessed using colorimetric assay kits. Furthermore, TLR4 and NF-κB protein expression was determined by western blot analysis. The results revealed that andrographolide reduced the proliferation, while increasing cellular apoptosis and caspase-9/3 activation of MM cells, in addition to downregulating the expression of TLR4 and NF-κB protein. Of note, TLR4- or NF-κB-targeting small-interfering (si)RNA enhanced the andrographolide-induced inhibition of cell proliferation and induction of apoptosis of MM cells. The results of the present study therefore suggested that andrographolide inhibited multiple myeloma cells via the TLR4/NF-κB signaling pathway.

摘要

穿心莲内酯是爵床科药用植物穿心莲[(Burm.f)Nees]提取物中的一种活性成分。药理学研究表明,穿心莲内酯具有抗菌、抗炎、抗病毒、免疫调节和保肝特性,在治疗心血管疾病方面有效,同时毒性低、成本低。本研究旨在确定穿心莲内酯对多发性骨髓瘤(MM)细胞生长的抑制作用及其对Toll样受体(TLR)4/核因子(NF)-κB信号通路的可能影响。使用MTT法检测细胞增殖,使用流式细胞术测量细胞凋亡,并使用比色法试剂盒评估caspase-9/3激活情况。此外,通过蛋白质印迹分析确定TLR4和NF-κB蛋白表达。结果显示,穿心莲内酯可降低MM细胞的增殖,同时增加细胞凋亡和caspase-9/3激活,此外还下调TLR4和NF-κB蛋白的表达。值得注意的是,靶向TLR4或NF-κB的小干扰(si)RNA增强了穿心莲内酯诱导的MM细胞增殖抑制和凋亡诱导。因此,本研究结果表明穿心莲内酯通过TLR4/NF-κB信号通路抑制多发性骨髓瘤细胞。

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