Effect of N-tosyl-L-phenylalnylchloromethyl ketone and dexamethasone on expression of nuclear transcription factor-kappaB in childhood acute lymphoblastic leukemia and its significance.
- Author:
Qig AN
1
;
Tian-Yang XUE
;
Wei XU
;
Ji-Zhao GAO
;
Yi WU
;
Chun-Pin XU
Author Information
1. Department of Hematology, Xuzhou Children Hospital, Xuzhou 221006, China.
- Publication Type:Journal Article
- MeSH:
Bone Marrow Cells;
pathology;
Cells, Cultured;
Child;
Child, Preschool;
Dexamethasone;
pharmacology;
Female;
Humans;
Infant;
Leukocytes, Mononuclear;
pathology;
Male;
NF-kappa B;
biosynthesis;
genetics;
Precursor Cell Lymphoblastic Leukemia-Lymphoma;
metabolism;
pathology;
Protein Synthesis Inhibitors;
pharmacology;
Tosylphenylalanyl Chloromethyl Ketone;
pharmacology;
Tumor Cells, Cultured
- From:
Journal of Experimental Hematology
2007;15(2):399-403
- CountryChina
- Language:Chinese
-
Abstract:
In order to investigate the effect of N-tosyl-L-phenylalnylchloromethyl ketone (TPCK) and dexamethasone (Dex) on expression of nuclear transcription factor-kappaB (NF-kappaB) in childhood acute lymphoblastic leukemia (ALL) and its significance, so as to provide the experimental basis for corresponding clinical treatment of ALL, in which NF-kappaB is taken as a target. The biotin-streptavidin method was used to detect the expression of NF-kappaB P65 protein and the effects of TPCK and Dex at clinically relevant dosage on activity of NF-kappaB P65 protein in 20 childhood ALL patients. The results indicated that the expression of NF-kappaB P65 protein was strongly diminished and reached to negative level at 2 hours by treatment with 40 micromol/L TPCK, the positive expression of NF-kappaB P65 protein was (2.5 +/- 1.6)%. TPCK had a time-dependent inhibitory effect on ALL cells cultured in vitro. The expression of NF-kappaB P65 protein in ALL cells was strongly inhibited by clinically relevant concentration of dexamethasone 5.0 microg/ml for 24 hours in vitro. The positive expression was (25.0 +/- 3.0)%, there was significant difference, as compared with untreated ALL cells (T=55, P<0.01). It is concluded that TPCK and Dex can inhibit NF-kappaB activity. Inhibition of NF-kappaB activity may be one of the effect mechanism of dexamethasone on ALL cells. Inhibition of NF-kappaB conduction pathway may have a significant value in childhood ALL treatment.
