苏林酸在NF-κB对人乳腺癌TNF-α诱导细胞凋亡增敏中的相关作用

Sulindac enhances sensitization effect of NF-κB on apoptosis induced by TNF-α in human breast cancer

目的探讨苏林酸在NF-κB对人乳腺癌TNF-α诱导细胞凋亡增敏中的相关作用。方法取对数生长期的人乳腺癌细胞系MCF-7,加入苏林酸,使其终浓度分别为0.5 mmol/L和1.0 mmol/L,并设不加苏林酸的对照组进行培养;苏林酸处理48 h后进行MTT、流式细胞实验和Western blot法检测,分析苏林酸对肿瘤细胞生长的作用与相关机制。结果 0.5 mmol/L和1.0 mmol/L苏林酸分别刺激MCF-7细胞48 h后,对应的MCF-7细胞的增殖抑制率为(29.17±1.23)%、(38.15±1.51)%,对照组为(1.15±0.02)%(P<0.05)。与对照组相比,0.5 mmol/L和1.0 mmol/L苏林酸作用后均可导致滞留在G0~G1期的MCF-7细胞显著增加(P<0.05);0.5 mmol/L和1.0 mmol/L苏林酸作用后MCF-7细胞的凋亡率明显增加(P<0.05);0.5 mmol/L和1.0 mmol/L苏林酸作用后TNF-α的相对表达量分别为2.09±0.67、1.18±0.09,明显低于对照组的7.42±0.56(P<0.05)。结论苏林酸具有一定抗人乳腺癌细胞生长的作用,能促使细胞周期G0~G1期延长,提高细胞凋亡增敏作用,其作用机制可能与抑制TNF-α活性有关。

Objective The objective of this study was to investigate the role of sulindac in sensitization effects of NF - κB on apoptosis induced by TNF - α in human breast cancer. Methods The human breast cancer MCF -7 cell line was added sulindal in the logarithmic growth phase and the final concentrations of sulindac were 0.5 and 1.0 mmol/L. The cells in control group was cultured without adding succinic acid. After sulindac treat-ment for 48 h,flow cytometry, MTT and Western blotting were used to analyze the effect and mechanism of cell growth in MCF -7 cells. Results The inhibitory rate of cell proliferation was（29. 17 ± 1 .2 3 ）% and （38. 15 ± 1.51）% in MCF -7 cells treated with 0. 5 and 1.0 mmol/L of Sulindac for 48 h, respectively, when compared to the control group（ 1. 15 ± 0. 02）% （P 〈0？ 05）. Compared with the control group,0. 5 and 1.0 mmol/L of sulin- dac were significantly increased the G0 /G1 phase in MCF- 7 cells（ P 〈0. 05 ） . The apoptosis rate of sulindac in MCF -7 cells was significantly higher than that in the control group（P 〈0. 05）. The expression levels of TNF - α were（2. 09 ±0. 67）% and（ 1.18 ±0. 09）% in the concentrations of 0. 5 and 1. 0mmol/L sulindac, respectively, in MCF-7 cells when compared to the control group（7. 42 ±0. 56）% . Conclusion Sulindac has a certain effect on the growth of human breast cancer cells,which can promote the prolongation of cell cycle at the G1 /G1 phase and improve sensitization of apoptosis. This mechanism may be related to the inhibition of TNF - α activity.