Effects Of 17 Beta-Estradiol And Tamoxifen On Gastric Cancer Cell Proliferation And Apoptosis And Er-Alpha 36 Expression

The present study aimed to investigate the effects of 17 beta-estradiol and tamoxifen, an agonist and inhibitor of the estrogen receptor (ER), respectively, on the proliferation and apoptosis of gastric cancer cells, as well as the messenger (m)RNA expression levels of ER-alpha 36. Nested reverse transcription-polymerase chain reaction (RT-PCR) confirmed that ER-alpha 36 was expressed in th(e) BGC823, MKN45 and SGC7901 human gastric cancer cell lines. Subsequently, the BGC823 cell line was stimulated with various concentrations of 17 beta-estradiol or tamoxifen for 24 or 48 h, and the proliferation, apoptosis and mRNA expression levels of ER-alpha 36 were determined by water-soluble tetrazolium (WST)-1 assay, flow cytometry and RT-quantitative PCR, respectively. The activity of BGC823 cells was significantly increased following treatment with 10(-12) mol/l 17 beta-estradiol for 24 h (P=0.013), as compared with the control, and reached a peak at 48 h (P=0.002). Notably, the activity of BGC823 cells was decreased with increasing concentrations of 17 beta-estradiol, although it remained higher compared with that of the control. In the tamoxifen-treated groups, the cell activity decreased as the drug concentration increased. The apoptosis rate was markedly reduced in the 17 beta-estradiol group after 24 h (10(-12) mol/l, P=0.013; 10(-11) mol/l, P=0.023; and 10(-10) mol/l, P=0.017) and after 48 h (10(-12) mol/l, P=0.002; 10(-11) mol/l, P=0.011; and 10(-10) mol/l, P=0.033), whereas the rate of apoptosis increased as the tamoxifen concentration increased (24 h: 5x10(-6) mol/l, P=0.002; and 10(-5) mol/l, P=0.001; and 48 h: 5x10(-6) mol/l, P=0.014 and 10(-5) mol/l, P=0.0021), as compared with the control group. The mRNA expression levels of ER-alpha 36 were significantly increased after 24 h of treatment with 10(-12) mol/l (P=0.024), 10(-11) mol/l (P=0.0113) and 10(-10) mol/l (P=0.0037) 17 beta-estradiol compared with the control group when the concentration of 17 beta-estradiol was low, and the same was observed after 48 h of treatment 10(-12) mol/l (P=0.0164), 10(-11) mol/l (P=0.0342) and 10(-10) mol/l (P=0.0198) 17 beta-estradiol. The mRNA expression levels of ER-alpha 36 were significantly decreased with increasing concentrations of tamoxifen after 24 h (5x10(-6) mol/l, P=0.0233; and 10(-5) mol/l, P=0.007) and after 48 h (5x10(-6) mol/l, P=0.001; and 10(-5) mol/l, P=0.0153). In addition, the ability of tamoxifen to inhibit the growth of gastric cancer cells was concentration-dependent. The results of the present study suggested that gastric cancer cells were sensitive to the effects of 17 beta-estradiol and tamoxifen, and that tamoxifen is able to induce gastric cancer cell apoptosis. The expression levels of ER-alpha 36 were upregulated, and the growth of gastric cancer cells was increased, following treatment with 17 beta-estradiol, thus suggesting that gastric cancer tumors are stimulated by estrogen.