[Effect of endogenous TGF-beta1 and TNF-alpha on the As(2)O(3) inducing apoptosis of HL-60 cells].
OBJECTIVE
To study the effect of endogenous TGF-beta(1) and TNF-alpha on As(2)O(3) inducing apoptosis of HL-60 cells.


METHODS
The expressions of endogenous TGF-beta(1) and TNF-alpha in apoptotic HL-60 cells induced by As(2)O(3) were assayed by RT-PCR, quantitative RT-PCR, ELISA, DNA fragmentation and TUNEL. The effect of TGF-beta(1) and TNF-alpha antisense phosphorothioate oligodeoxynucleotides (PSODNs) on As(2)O(3) inducing apoptotic HL-60 cells was further studied.


RESULTS
(1) Expressions of endogenous TGF-beta(1) and TNF-alpha were significantly up-regulated in As(2)O(3) inducing apoptotic HL-60 cells (from 13,546 +/- 124 and 497,216 +/- 187 before treatment to 23,273 +/- 229 and 674,217 +/- 189 after treatment, respectively), accompanied with down-regulated bcl-2 mRNA expression (from 10,424 +/- 274 before treatment to 3,361 +/- 89 after treatment). (2) TGF-beta(1) and TNF-alpha antisense PSODNs could rescue As(2)O(3) induced apoptosis of HL-60 cells, with a restoration of bcl-2 gene expression.


CONCLUSIONS
Endogenous TGF-beta(1) and TNF-alpha played an important role in As(2)O(3) inducing HL-60 cells apoptosis through down-regulation of bcl-2 expression.
Chen
Yuan-zhong
YZ
Fujian Institute of Hematology, Union Hospital, Fujian Medical University, Fuzhou 350001, China.
Wu
Yong
Y
Huang
Mei-juan
MJ
Lu
Lian-huang
LH
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D015536:Down-Regulation; D018922:HL-60 Cells; D006801:Humans; D010087:Oxides / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D000077237:Arsenic Trioxide