17β-雌二醇睾酮三苯氧胺和氨鲁米特对肺腺癌细胞株A549生长增殖的影响

Effects of 17β-estrogen, testosterone, tamoxifen, and aminoglutethimide on the growth and proliferation of lung adenocarcinoma cell line A549

目的 检测肺腺癌细胞株A5 49芳香化酶蛋白表达 ,并探讨 17β 雌二醇 (estrogen ,E2 )、睾酮 (testosterone ,T)、雌激素受体拮抗剂三苯氧胺 (tamoxifen ,TAM)和芳香化酶抑制剂氨鲁米特 (DL Aminoglutethimide ,AMIN)对A5 49细胞生长增殖的影响。方法 采用免疫组织化学法检测A5 49细胞株芳香化酶蛋白的表达 ,用流式细胞仪和四唑氮法测定加入E2 、T、TAM和AMIN前后细胞周期和细胞数量的变化。结果 A5 49细胞芳香化酶蛋白表达阳性。芳香化酶抑制剂AMIN和 5× 10 - 7mol L的TAM可抑制A5 49细胞的生长 ,使之阻滞于G0 G1 期 (P <0 0 1和P <0 0 0 1)。当将TAM的浓度提高至 5×10 - 6 mol L ,3d后G2 M期细胞明显减少 ,S期细胞明显增多 (P <0 0 0 1) ;与对照组相比 ,E2 和T均能促进A5 49细胞的生长(P <0 0 1和P <0 0 5 ) ;而单独应用TAM或AMIN则可抑制A5 49细胞的生长 (P <0 0 1和P <0 0 5 ) ,且两者可分别抑制E2和T对A5 49细胞的促生长作用 (P <0 0 1)。结论 E2 和T对A5 49细胞有促生长作用 ,TAM和AMIN能抑制A5 49的生长增殖 ,且可拮抗E2

Objective To determine the aromatase protein expression in A549 cell and to investigate the effects of 17β estrogen (E 2), testosterone (T), estrogen receptor antagonist tamoxifen (TAM), and aromatase inhibitor DL aminoglutethimide (AMIN) on the growth and proliferation of A549 cells. Methods The expression of aromatase protein was determined by immunohistochemical methods. The changes of cell cycle and cell number before and after treatment with E 2, T, TAM, and AMIN were measured by flow cytometry and tetrazolium method (MTT). Results The aromatase protein was positively expressed in A549 cells. The aromatase inhibitor AMIN and 5×10 -7 mol/L TAM could inhibit the growth of A549 cells and block them in G 0/G 1 phase ( P <0.01 or P <0.001). Significantly decreased cells in G 2/M phase but increased cells in S phase were found at 3 d after the concentration of TAM was increased up to 5×10 -6 mol/L ( P <0.001). Compared with the control group, both E 2 and T could promote the growth of A549 cells ( P <0.01 and P <0.05), but TAM or AMIN alone could inhibit the growth of A549 cells ( P <0.01 and P <0.05). Either TAM or AMIN could inhibit the promoting effect of E 2 and T on the growth of A549 cells ( P <0.01) . Conclusion E 2 and T have promoting effect on the growth of A549 cells. TAM and AMIN can inhibit the growth and proliferation of A549 cells and antagonize the effect of E 2 and T.