重组人转化生长因子-β1 或/和白细胞介素-6 对人白血病细胞生长抑制及原癌基因 c-myc 表达的影响
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.
作者信息
Feng R, Shen S, Hui H, Jin M
机构信息
Department of Haematology, Nanfang Hospital, First Military Medical University, Guangzhou, China.
出版信息
Chin Med J (Engl). 1997 Nov;110(11):847-50.
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.
目的
研究重组人转化生长因子-β1（rhTGF-β1）单独作用、重组人白细胞介素-6（rhIL-6）单独作用或二者联合作用对人白血病细胞系增殖抑制的影响。
方法
在本研究中，以人单核细胞系（U937）和人早幼粒细胞系（HL60）作为体外模型，我们用3H-TdR掺入率、细胞DNA含量、DNA指数、细胞周期及c-myc mRNA表达分析两种细胞因子对增殖抑制的影响。
结果
给予rhTGF-β1和rhIL-6后，U937细胞生长受到抑制，3H-TdR掺入抑制率增加。细胞DNA含量和DNA指数降低。给予rhTGF-β1或rhIL-6后细胞周期未观察到变化。然而，给予rhTGF-β1和rhIL-6联合用药后，G0/G1期细胞增加，G2M+S期细胞减少。还发现rhIL-6可抑制HL60细胞的增殖反应，同时rhTGF-β1可增强这种抑制作用。rhIL-6加rhTGF-β1诱导后，3H-TdR掺入抑制率升至39.89%，DNA指数降至1.00。此外，G0/G1期细胞增加，G2M+S期细胞减少。
结论
这些结果表明，rhTGF-β1和rhIL-6联合作用具有协同效应，可抑制U937和HL60细胞系的增殖。分子杂交试验表明，rhTGF-β1单独作用、rhIL-6单独作用或rhTGF-β1与rhIL-6联合作用均可时间和剂量依赖性地抑制U937和HL60细胞c-myc mRNA的表达。rhTGF-β1和rhIL-6联合作用协同抑制c-myc表达，这可能是这两种细胞因子发挥作用的机制之一。
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