Effects of recombinant human transforming growth factor-beta 1 or/and interleukin-6 on growth inhibition and proto-oncogene c-myc expression in human leukemia cells.
OBJECTIVE
To examine the effect of recombinant human transforming growth factor-beta 1 (rhTGF-beta 1) alone or recombinant human interleukin 6 (rhIL-6) alone or in combination on proliferation inhibition of the human leukaemia cell line.


METHODS
In the present study, using the human monoblastic cell line (U937) and human promyelocytic cell line (HL60) as an in vitro model, we analyzed the effect of two cytokins on proliferation inhibition with rate of 3H-TdR incorporation, the cellular content of DNA, DNA indices, the cell cycle and the expression of c-myc mRNA.


RESULTS
With administration of rhTGF-beta 1 and rhIL-6, U937 cell growth was inhibited and the rate of 3H-TdR incorporation inhibition was increased. There was a decrease in the cellular content of DNA and DNA indices. And no change in the cell cycle was observed after administration of rhTGF-beta 1 or rhIL-6. However, there was an increase in G0/G1 phase cells and a decrease in G2M + S phase cells after administration of combination of rhTGF-beta 1 and rhIL-6. It was also found that rhIL-6 could inhibit proliferative responses of HL60 cells, meanwhile the inhibition could be enhanced by rhTGF-beta 1. The rate of 3H-TdR incorporation inhibition rose up to 39.89%, and DNA index fell to 1.00 following induction by rhIL-6 plus rhTGF-beta 1. Furthermore, G0/G1 phase cells increased while G2M + S cells decreased.


CONCLUSIONS
These results suggest that combination of rhTGF-beta 1 and rhIL-6 acted in synergy to inhibit proliferation of both U937 and HL60 cell lines. Molecular hybridization test show that rhTGF-beta 1 alone, rhIL-6 alone or rhTGF-beta 1 and rhIL-6 in combination can inhibit U937 and HL60 cells expression of c-myc mRNA in a time and dose dependent manner. rhTGF-beta 1 and rhIL-6 in combination synergistically inhibited c-myc expression, which may be one of the machanisms for the actions of the two cytokines.
Feng
R
R
Department of Haematology, Nanfang Hospital, First Military Medical University, Guangzhou, China.
Shen
S
S
Hui
H
H
Jin
M
M
D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D015870:Gene Expression; D016259:Genes, myc; D018922:HL-60 Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D007938:Leukemia / Q000473:pathology*; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D015850:Interleukin-6; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta