[Effect of N-tosyl-L-phenylalnylchloromethyl ketone and dexamethasone on expression of nuclear transcription factor-kappaB in childhood acute lymphoblastic leukemia and its significance].
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.
An
Qig
Q
Department of Hematology, Xuzhou Children Hospital, Xuzhou 221006, China.
Xue
Tian-Yang
TY
Xu
Wei
W
Gao
Ji-Zhao
JZ
Wu
Yi
Y
Xu
Chun-Pin
CP
D001854:Bone Marrow Cells / Q000473:pathology; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000096:biosynthesis* / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism* / Q000473:pathology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D016328:NF-kappa B; D011500:Protein Synthesis Inhibitors; D014108:Tosylphenylalanyl Chloromethyl Ketone; D003907:Dexamethasone