Danforth D N, Sgagias M K
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Cancer Res. 1993 Apr 1;53(7):1538-45.
We studied the effects of interleukin-1 alpha (IL-1) and interleukin-6 (IL-6) on MCF-7 breast cancer cells to determine whether these cytokines act additively/synergistically to alter cell growth and metabolism. We found that IL-1 alone (1000 units/ml) inhibited cell growth to a greater degree (83.8%) than IL-6 alone (29.2%, P < 0.001). The combination of IL-1 + IL-6 caused greater inhibition of growth (92.9%, P < 0.02) than either cytokine alone. The additive effect was dose dependent for both IL-1 and IL-6. IL-1 and IL-6 also antagonized estradiol (10(-9) M) stimulated growth. Antagonism by the combination was greater than for either cytokine alone (P < 0.001). IL-1 or IL-6 alone each down-regulated the estrogen receptor (36.7%, P < 0.01, and 23.2%, P < 0.05, respectively), but the combination IL-1 + IL-6 did not cause a significantly greater effect than IL-1 alone. Neither IL-1 or IL-6 blocked estradiol stimulation of progesterone receptor (PR) synthesis; however, the combination IL-1 + IL-6 increased PR content by 28.4% (P < 0.01). IL-1, but not IL-6, increased secretion of transforming growth factor-beta (TGF-beta) by 2.45-fold over 72 h (P < 0.01). The increase was time dependent (detectable at 24 h) and dose dependent (maximum increase of 5.3-fold, 10,000 units/ml, P < 0.02). IL-1-induced TGF-beta secretion was blocked by estradiol (10(-9) M). Neither cytokine altered secretion of insulin-like growth factor-1. These findings indicate that IL-1 and IL-6 act additively to inhibit growth in the absence or presence of estradiol and modulate the estrogen receptor and progesterone receptor content of these cells. TGF-beta may mediate the effects of IL-1; however, other pathways appear to be required for the additive effects of these cytokines.
我们研究了白细胞介素 -1α（IL -1）和白细胞介素 -6（IL -6）对MCF -7乳腺癌细胞的影响，以确定这些细胞因子是否以相加/协同的方式作用来改变细胞生长和代谢。我们发现，单独使用IL -1（1000单位/毫升）比单独使用IL -6（29.2%，P < 0.001）对细胞生长的抑制程度更大（83.8%）。IL -1 + IL -6联合使用对生长的抑制作用（92.9%，P < 0.02）比单独使用任何一种细胞因子都更强。IL -1和IL -6的相加作用呈剂量依赖性。IL -1和IL -6还拮抗雌二醇（10⁻⁹ M）刺激的生长。联合使用的拮抗作用比单独使用任何一种细胞因子都更强（P < 0.001）。单独使用IL -1或IL -6各自下调雌激素受体（分别为36.7%，P < 0.01和23.2%，P < 0.05），但IL -1 + IL -6联合使用与单独使用IL -1相比，并未产生显著更大的效果。IL -1和IL -6均未阻断雌二醇对孕激素受体（PR）合成的刺激；然而，IL -1 + IL -6联合使用使PR含量增加了28.4%（P < 0.01）。IL -1而非IL -6在72小时内使转化生长因子 -β（TGF -β）的分泌增加了2.45倍（P < 0.01）。这种增加是时间依赖性的（在24小时可检测到）且呈剂量依赖性（最大增加5.3倍，10000单位/毫升，P < 0.02）。IL -1诱导的TGF -β分泌被雌二醇（10⁻⁹ M）阻断。两种细胞因子均未改变胰岛素样生长因子 -1的分泌。这些发现表明，在有或没有雌二醇存在的情况下，IL -1和IL -6以相加的方式作用来抑制生长，并调节这些细胞的雌激素受体和孕激素受体含量。TGF -β可能介导IL -1的作用；然而，这些细胞因子的相加作用似乎还需要其他途径。
