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KMID : 1094020110280060549
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Journal of Veterinary Clinics
2011 Volume.28 No. 6 p.549 ~ p.554
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Antagonic Effects of Dexamethasone on FK506-induced Antitumor Effects in Hep3B Cells
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Park Hye-Min
Lee Sei-Jin
Kim Sun-Young
Go Hyeon-Kyu
Jeon Seol-Hee
Kim Shang-Jin
Kim Jin-Shang
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Abstract
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FK506 is a widespread immunosuppressive drug after liver transplantion in patients with advanced-stage hepatocellular carcinoma. Dexamethasone is frequently used as co-treatment in cytotoxic cancer therapy, e.g. to prevent nausea, to protect normal tissue or for other reasons. Our aim was to investigate antitumor effects of FK506 in Hep3B cells, one of differentiated human hepatocellular carcinoma cell lines and inhibitory effects of dexamethsone on FK506-induced antitumor effects. Cell injury was evaluated by biochemical assays as cell viability, lactate dehydrogenase (LDH) and reactive oxygen species (ROS) in Hep3B cells. Intracellular calcium concentration ([Ca2+]i) and the level of activation of the c-Jun-N-terminal kinase (JNK) and the Bax protein in cultured Hep3B cells was measured. Exposure of 0.1 μM FK506 to Hep3B cells led to cell death accompanied by a decrease in cell viability and an increase in LDH, ROS and [Ca2+]i. FK506 induced an increase in activity of Bax and JNK protein but inhibited the activity ofBcl-2 protein. Treatment of dexamethsone, per se, had no effects on cell viability, LDH and ROS. However, co-treatment of FK506 and dexamethasone diminished the FK506-induced LDH release, ROS generation and JNK activation. These results demonstrate that FK506 has antitumor effect in Hep3B cells but the combination of FK506 and dexamethasone antagonizes the FK506-induced antitumor effects.
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KEYWORD
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hepatocellular carcinoma cell line (Hep3B), FK506, dexamethasone
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