一种肝脏衍生生长抑制剂、转化生长因子β1和重组肿瘤坏死因子α在正常细胞和肿瘤细胞中的生长调节作用。

Growth modulatory effects of a liver-derived growth inhibitor, transforming growth factor beta 1, and recombinant tumor necrosis factor alpha, in normal and neoplastic cells.

作者信息

Chapekar M S, Huggett A C, Thorgeirsson S S

机构信息

Division of Cancer Etiology, National Cancer Institute, Bethesda, Maryland 20892.

出版信息

Exp Cell Res. 1989 Nov;185(1):247-57. doi: 10.1016/0014-4827(89)90053-0.

DOI:10.1016/0014-4827(89)90053-0

PMID:2806409

Abstract

The growth modulatory effects of a rat liver-derived growth inhibitor (LDGI), transforming growth factor beta 1 (TGF-beta 1), and recombinant tumor necrosis factor (rTNF-alpha) were examined in a variety of liver-derived and nonliver-derived normal and neoplastic cell culture systems. Normal rat liver epithelial (RLE) cells were highly sensitive to the growth inhibitory effects of LDGI (ID50 = 0.2 ng/ml) and TGF-beta 1 (ID50 = 0.25 ng/ml) but were less sensitive to rTNF-alpha (ID40 = 5000 Units/ml). Aflatoxin B1-transformed RLE cells showed sensitivity to the cytostatic effects of LDGI (ID50 = 1.5 ng/ml); however, these cells were completely resistant to the antiproliferative effects of TGF-beta 1 and rTNF-alpha. Clones isolated from these transformed cells, exhibited a wide range of sensitivities to LDGI but all of the clones were resistant to the growth inhibitory effects of both TGF-beta 1 and rTNF-alpha. Rat hepatoma Reuber cells were extremely sensitive to the antiproliferative effects of rTNF-alpha (ID50 = 10 Units/ml) but exhibited sensitivity to LDGI only at concentrations above 1.5 ng/ml and were resistant to the antiproliferative effects of TGF-beta 1. Rat hepatoma UVM 7777 cells and human hepatoma HepG2 cells, however, were insensitive to the growth inhibitory effects of all three factors. Among the nonliver-derived cells, human breast carcinoma (MCF-7) cells were extremely sensitive to rTNF-alpha (ID50 = 20 Units/ml, exhibited some sensitivity to LDGI (ID50 = 1 ng/ml), and were resistant to the antiproliferative effects of TGF-beta 1. In contrast, the rate of DNA synthesis is rat kidney fibroblasts and human foreskin fibroblasts was significantly stimulated in response to TGF-beta 1, LDGI, and rTNF-alpha. These data demonstrate that LDGI, TGF-beta 1, and rTNF-alpha exert positive and negative modulations of growth in different cell systems and that the growth regulatory effects of LDGI differ from those of TGF-beta 1 and rTNF-alpha in some cell types.

摘要

在多种源自肝脏和非肝脏的正常及肿瘤细胞培养系统中，研究了大鼠肝脏衍生生长抑制剂（LDGI）、转化生长因子β1（TGF-β1）和重组肿瘤坏死因子（rTNF-α）的生长调节作用。正常大鼠肝脏上皮（RLE）细胞对LDGI（半数抑制浓度ID50 = 0.2 ng/ml）和TGF-β1（ID50 = 0.25 ng/ml）的生长抑制作用高度敏感，但对rTNF-α较不敏感（半数抑制浓度ID40 = 5000 Units/ml）。黄曲霉毒素B1转化的RLE细胞对LDGI的细胞生长抑制作用敏感（ID50 = 1.5 ng/ml）；然而，这些细胞对TGF-β1和rTNF-α的抗增殖作用完全耐药。从这些转化细胞中分离出的克隆对LDGI表现出广泛的敏感性，但所有克隆对TGF-β1和rTNF-α的生长抑制作用均耐药。大鼠肝癌Reuber细胞对rTNF-α的抗增殖作用极其敏感（ID50 = 10 Units/ml），但仅在浓度高于1.5 ng/ml时对LDGI敏感，对TGF-β1的抗增殖作用耐药。然而，大鼠肝癌UVM 7777细胞和人肝癌HepG2细胞对所有三种因子的生长抑制作用均不敏感。在非肝脏来源的细胞中，人乳腺癌（MCF-7）细胞对rTNF-α极其敏感（ID50 = 20 Units/ml），对LDGI表现出一定敏感性（ID50 = 1 ng/ml），对TGF-β1的抗增殖作用耐药。相反，大鼠肾成纤维细胞和人包皮成纤维细胞的DNA合成速率在受到TGF-β1、LDGI和rTNF-α刺激后显著增加。这些数据表明，LDGI、TGF-β1和rTNF-α在不同细胞系统中对生长发挥正负调节作用，且LDGI在某些细胞类型中的生长调节作用与TGF-β