[Combined effect of recombinant mutant human TRAIL and daunorubicin in inducing apoptosis of leukemia cell and its mechanism].
The aim of study was to investigate the combined effect of recombinant mutant human TRAIL (rmhTRAIL) with daunorubicin (DNR) or alone on K562 and U937 leukemia cell lines and its mechanism. The fibroblasts (MRC-5) of normal-human embryonic lung were used as control cells. After being treated with rmhTRAIL and DNR or only with rmTRAIL, the cytotoxic effect and the apoptosis rate in K562, U937 cells were measured by MTT assay. The expression levels of TRAIL death receptor and TRAIL decoy receptor mRNA in these three cell lines were assayed by semiquantitive RT-PCR before and after treatment with DNR. The results indicated that K562 and U937 were sensitive to rmhTRIAL. DNR had synergistic inhibitory effect with rmhTRAIL on the growth of K562 and U937 cell lines (P < 0.05). The expression level of DR4 and DR5 mRNA was significantly higher in K562 and U937 with combined treatment of rmhTRAIL and DNR than that in those alone, while the expressions of DcR1 and DcR2 mRNA were not influenced. It is concluded that in vitro, rmhTRAIL alone or in combination with DNR can obviously inhibit the growth of leukemia cell lines and induce cell apoptosis, DNR and rmhTRAIL have a synergistic inhibitory effect on growth of K562 and U937. The mechanism may correlate with the up-regulation of DR4 and DR5 of K562 and U937.
Zhang
Xue-Jun
XJ
Department of Hematology, The second Hospital, Hebei Medical University, Shijiazhuang 050000, China. zhang_xuejun8@yahoo.com.cn
Wen
Li
L
Wang
Fu-Xu
FX
Luo
Jian-Min
JM
Pan
Ling
L
Liu
Xiao-Jun
XJ
DU
Xing-Yan
XY
Dong
Zuo-Ren
ZR
Yang
Shi-Fang
SF
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D003630:Daunorubicin / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D020014:K562 Cells; D009154:Mutation; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D020298:U937 Cells; D015854:Up-Regulation
D000903:Antibiotics, Antineoplastic; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; D003630:Daunorubicin