Synergistic effect of 17-allylamino-17-demethoxygeldanamycin with dehydroxymethylepoxyquinomicin on the human anaplastic thyroid carcinoma cell line KTC2

Archives of Biological Sciences

卷:73

Stamenković Gorana¹  Umezawa Kazuo²  Yamashita Shunichi³  Vučetić-Tadić Biljana⁴  Stanojević Boban⁵  Todorović Lidija⁶  Božović Ana⁶ 

[1] Department of Genetic Research, Institute for Biological Research “Siniša Stanković”, National Institute of thе Republic of Serbia, University of Belgrade, Belgrade, Serbia;

[2] Department of Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan + Department of Molecular Target Medicine, Aichi Medical University, Nagakute, Japan;

[3] Department of Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan + Fukushima Medical University, Fukushima, Japan;

[4] Institute for Mother and Child Healthcare of Serbia, Belgrade, Serbia;

[5] Laboratory for Radiobiology and Molecular Genetics, Vinča Institute of Nuclear Sciences, National Institute of thе Republic of Serbia, University of Belgrade, Belgrade, Serbia + Department of Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan;

[6] Laboratory for Radiobiology and Molecular Genetics, Vinča Institute of Nuclear Sciences, National Institute of thе Republic of Serbia, University of Belgrade, Belgrade, Serbia;

关键词: nf-κb inhibitor;    hsp90 inhibitor;    synergy;    targeted inhibitor;    combined treatment;   

DOI  :  10.2298/ABS201010055T

来源: DOAJ

【 摘 要 】

The use of targeted inhibitors has shown promise as an effective approach in cancer therapy. However, targeted therapies based only on one drug, such as 17-allylamino-17-demethoxygeldanamycin (17-AAG), have limited success, partly because cancer cells engage alternate pathways for survival and proliferation. In the present study, we evaluated whether dehydroxymethylepoxyquinomicin (DHMEQ), a nuclear factor κB (NF-κB) inhibitor, can enhance the antitumor activities of 17-AAG, a 90 kDa heat shock protein (Hsp90) inhibitor, in the anaplastic thyroid cancer cell line KTC2. We examined the effect of combined drug treatment vs single drug treatment on cell survival. Isobologram analysis was performed to distinguish the additive vs synergistic effects of the drug combination. Western blotting was performed to investigate apoptosis markers: caspase 3, poly(ADP-ribose) polymerase-one (PARP-1), B-cell lymphoma-extra large (Bcl-XL), X-linked inhibitor of apoptosis (XIAP) and cellular inhibitor of apoptosis 2 (cIAP-2). Compared to monotherapy, the combined treatment enhanced growth-inhibitory effects in a synergistic manner and strongly potentiated apoptosis. These results demonstrate the first in vitro evidence that a combination of Hsp90 and NF-κB inhibitors is a more effective modality for inhibiting cell proliferation and survival in anaplastic thyroid carcinoma cells than either agent alone, warranting further investigations.

【 授权许可】

Unknown