血清对全反式视黄酸抑制肺癌细胞生长的影响

Effect of Serum on the Growth Inhibition of Lung Cancer Cells by All-trans Retinoic Acid

研究不同浓度的血清对全反式视黄酸 (ATRA)抑制肺癌细胞生长的影响 .当细胞培养在 10 %血清中 ,ATRA不能抑制肺癌细胞生长 ,但是当细胞培养在 1%血清中 ,ATRA能够有效地抑制肺癌细胞生长 .视黄酸受体RARβ介导视黄酸的抗癌作用 .Northern印迹分析表明 ,在高浓度血清中AT RA不能诱导RARβ表达 ,但在低浓度血清中ATRA可以诱导RARβ表达 ,并且瞬时转染和CAT测定证实是通过激活RABβ启动子转录活性而诱导RARβ表达的 .孤生受体Nur77受到血清生长因子刺激后会大量表达 ,具有抗视黄酸活性的作用 .肺癌细胞培养在低浓度血清中 ,Nur77mRNA低水平表达和Nur77蛋白不表达 .然而在高浓度血清中 ,Nur77mRNA和蛋白高水平表达 .另外 ,在无血清条件下 ,EGF也可以诱导Nur77表达 .结果提示 ,血清中的生长因子可能拮抗ATRA抑制肺癌细胞生长的作用 ,其作用途径可能是通过刺激细胞中Nur77表达 。

The effects of serum concentration on growth inhibition of lung cancer cells by all trans retinoic acid(ATRA)were investigated.It was found that lung cancer cells,H292 and H460,were resistant to ATRA effect on their growth inhibitions when cells were cultured in 10% serum medium.However,the growth of cells was inhibited by ATRA while the cells were cultured in 1% serum medium.Northern blot showed that RARβ(retinoic acid receptor β),which is associated with anti cancer of ATRA,was induced by ATRA at low serum concentration through activation of transcriptional activities of RARβ promoter and βRARE(β retinoic acid response element),revealed by transient transfection and CAT assay,but was not induced at high serum concentration.Orphan receptor Nur77,which is rapidly induced by serum growth factors and is involved in retinoic acid resistance,was expressed in mRNA and protein levels at high serum concentration,detected by Northern blot and Western blot,but not expressed in protein level and expressed at low level of mRNA at low serum concentration in lung cancer cells.In addition,EGF also induced Nur77 expression in lung cancer cells under the condition of serum free.Taken together,the data indicated that some of growth factors presented in serum might antagonize the effect of ATRA on growth inhibition of lung cancer cells.The pathway for serum action is likely to stimulate expression of Nur77 by some growth factors in serum,or suppress expression of RARβ through down regulation of transcriptional activity of RARβ promoter.