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Open Access Research

Combined effects of 17-DMAG and TNF on cells through a mechanism related to the NF-kappaB pathway

Zhuling Qu*, He Dong*, Xiaolin Xu, Wei Feng and Xuanlong Yi

Author Affiliations

The Affiliated Hospital of Medical College, Qingdao University, Qingdao, Shandong province 266021, China

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Diagnostic Pathology 2013, 8:70  doi:10.1186/1746-1596-8-70

Published: 1 May 2013

Abstract

Objective

The tumor necrosis factor (TNF) and the cellular NF-κB pathway protein IKKβ play important roles in various cellular processes such as cell proliferation, survival, differentiation, and apoptosis. A heat shock protein 90 inhibitor, 17-DMAG, can induce apoptosis of some tumor cells. This study is to determine the combined effects of 17-DMAG and TNF on malignant cells and the related mechanisms.

Methods

We have determined effects of 17-DMAG, an Hsp90 inhibitor, and TNF treatments on the small cell lung cancer cell line (MS-1), the adenocarcinoma cell line (A549), the squamous-cell carcinoma cell line (LK-2), and the normal human bronchial epithelium cell line (NuLi-1) by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrozolium bromide assay. To determine if 17-DMAG inhibit the expression of IKKβ in the normal human NuLi-1 cells, and the malignant MS-1, A549, and LK-2 cells, immunoblotting assays and luciferase assays were performed.

Results

It was found that the combined treatments resulted in synergistic killing of malignant cells, which was confirmed by the apoptosis determination using a fluorescence microscopic assay following staining of the drug-treated cells with Hoescht 33258. The immunoblotting results indicated that the synergistic killing due to 17-DMAG and TNF treatments may be related to the decreases in IKKβ levels in the presence of 17-DMAG.

Conclusions

The results suggest that combination of 17-DMAG and TNF treatments might be useful for treating malignancies upon further study in the further.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2041198513886824 webcite

Keywords:
17-DMAG; IKKβ; TNF; NF-κB Pathway