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The in vitro and in vivo anti-metastatic efficacy of oxythiamine and the possible mechanisms of action

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Abstract

This study examined the anti-metastatic effects of oxythiamine (OT) both in cell culture and in vivo. Cell culture results revealed that OT (0–20 μM) significantly inhibited the invasion and migration (IC50 = 8.75 μM) of Lewis lung carcinoma (LLC) cells. These effects of OT were accompanied by the inhibition of metalloproteinases-2 and -9 (MMP-2, MMP-9), urokinase-type plasminogen activator (uPA) activities and by the increases in protein expression of tissue inhibitors of metalloproteinases-1 and -2 (TIMP-1, TIMP-2). We then implanted (s.c.) C57BL/6 mice with LLC cells and supplemented the mice with a low- or a high-dose of OT (250 or 500 mg/kg BW) daily for 5 wk. During the 5-wk period, OT supplementation decreased plasma MMP-2 activity in a dose-dependent manner, and this effect was significant after 4 wk of tumor cell implantation. Tumor metastasis was found to confine to the lungs of mice injected with the tumor cells. High-OT supplementation strongly lowered the number and area of tumors and inhibited protein expression of MMP-2 and MMP-9 in the lungs. In addition, high-OT supplementation markedly decreased the extent of proliferating cell nuclear antigen (PCNA) staining in the lungs. By contrast, OT supplementation increased TIMP-1 and -2 protein expression in the lungs. These results demonstrate that OT supplementation attenuates tumor cell metastasis, possibly via inhibition of protein expression of MMPs, extent of PCNA staining and via increase of proteins expression of TIMPs.

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Abbreviations

LLC:

Lewis lung carcinoma

MMP:

Metalloproteinase

OT:

Oxythiamine

PCNA:

Proliferating cell nuclear antigen

PPP:

Pentose phosphate pathway

TK:

Transketolase

TIMP:

Tissue inhibitors of metalloproteinase

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Authors and Affiliations

  1. Department of Food Science and Biotechnology, National Chung Hsing University, 250 Kuo Kuang Road, Taichung, 402, Taiwan, ROC

    Chih-Min Yang, Yi-Zih Liu & Miao-Lin Hu

  2. Graduate Institute of Veterinary Pathobiology, National Chung Hsing University, 250 Kuo Kuang Road, Taichung, 402, Taiwan, ROC

    Jiunn-Wang Liao

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  1. Chih-Min Yang
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  2. Yi-Zih Liu
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  3. Jiunn-Wang Liao
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  4. Miao-Lin Hu
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Correspondence to Miao-Lin Hu.

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Yang, CM., Liu, YZ., Liao, JW. et al. The in vitro and in vivo anti-metastatic efficacy of oxythiamine and the possible mechanisms of action. Clin Exp Metastasis 27, 341–349 (2010). https://doi.org/10.1007/s10585-010-9331-2

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  • DOI: https://doi.org/10.1007/s10585-010-9331-2

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