Thibout D, Di Benedetto M, Kraemer M, Sainte-Catherine O, Derbin C, Crépin M
Laboratoire d'Oncologie des Tumeurs-SMBH 74, Université de Paris XIII, Bobigny, France.
Anticancer Res. 1998 Jul-Aug;18(4A):2657-61.
Sodium Phenylacetate (NaPq) has been shown to suppress tumor growth and promote differentiation in experimental models. Thus, we have previously shown an inhibition of MCF-7ras cell proliferation by NaPa both in vitro and in vivo on xenographed tumors. In order to study the action of NaPa on the synthesis of paracrine or autocrine growth factors, conditioned media were prepared from breast pretumoral HBL100 cells, tumoral MCF-7 and MCF-7ras cells in the presence of NaPa. Growth factor activities of these media were tested on Balb c/3T3 fibroblasts and on the above breast tumor cells. Conditioned media from the 3 cell types contained different mitogenic activities when tested on the same cell lines. NaPa treatment for 24 hours inhibited differentially and dose-dependently the mitogenic activity of conditioned media. Inhibitions of HBL100 and MCF-7 cell proliferation by MCF-7ras medium conditioned with 20 mM NaPa reached 75% and 48% respectively. In contrast, NaPa treated MCF-7 conditioned medium decreased HBL100 and MCF-7ras proliferation by 49% and 72%, respectively, at the same NaPa concentration. The efficiency of NaPa inhibition reached an optimum as soon as one day after treatment. Among growth factors secreted by MCF-7 and MCF-7ras, TGF beta synthesis is inhibited and stimulated in MCF-7 and MCF-7ras cells respectively after NaPa treatment. We showed that NaPa modifies the synthesis of growth factors secreted by MCF-7 and MCF-7ras tumor cells leading to cell proliferation inhibitions. The synthesis of these previously identified factors was more involved in MCF-7 cells than fibroblast cell proliferation. In vitro and in vivo NaPa inhibition of MCF-7ras cells which secreted higher levels of these growth factors could be explained by this mechanism of action.
苯乙酸钠（NaPq）在实验模型中已显示出抑制肿瘤生长并促进分化的作用。因此，我们之前已经证明，NaPa在体外和体内对异种移植肿瘤均能抑制MCF - 7ras细胞增殖。为了研究NaPa对旁分泌或自分泌生长因子合成的作用，在有NaPa存在的情况下，从乳腺肿瘤前HBL100细胞、肿瘤性MCF - 7和MCF - 7ras细胞制备条件培养基。在Balb c/3T3成纤维细胞和上述乳腺肿瘤细胞上测试这些培养基的生长因子活性。当在相同细胞系上测试时，来自这3种细胞类型的条件培养基具有不同的促有丝分裂活性。NaPa处理24小时以剂量依赖性方式差异抑制条件培养基的促有丝分裂活性。用20 mM NaPa处理的MCF - 7ras条件培养基对HBL100和MCF - 7细胞增殖的抑制分别达到75%和48%。相反，在相同NaPa浓度下，经NaPa处理的MCF - 7条件培养基使HBL100和MCF - 7ras增殖分别降低49%和72%。NaPa抑制的效率在处理后一天就达到最佳。在NaPa处理后，MCF - 7和MCF - 7ras分泌的生长因子中，TGFβ合成在MCF - 7细胞中受到抑制，而在MCF - 7ras细胞中受到刺激。我们表明，NaPa改变了MCF - 7和MCF - 7ras肿瘤细胞分泌的生长因子的合成，从而导致细胞增殖受到抑制。这些先前鉴定的因子的合成在MCF - 7细胞中比在成纤维细胞增殖中更起作用。这种作用机制可以解释NaPa在体外和体内对分泌较高水平这些生长因子的MCF - 7ras细胞的抑制作用。
