Liu Jun-Feng, Jamieson Glyn G, Drew Paul A, Zhu Gui-Jun, Zhang Shao-Wei, Zhu Tie-Nian, Shan Bao-En, Wang Qi-Zhang
Department of Thoracic Surgery, Fourth Hospital, Hebei Medical University, Shijiazhuang, China.
ANZ J Surg. 2005 Nov;75(11):1011-6. doi: 10.1111/j.1445-2197.2005.03596.x.
Aspirin has potential in the prevention or treatment of oesophageal cancer, the seventh most common cancer in the world, but its mechanism of action is still not certain.
The oesophageal squamous cell carcinoma cell line TE-13 was cultured with aspirin at different concentrations or for different times. Proliferation and apoptosis were measured by MTT reduction and flow cytometry. Expression of COX-2 mRNA was measured by RT-PCR and COX-2 protein levels with Western blot analysis. Nuclear NF-kappaB and cytoplasmic IkappaB protein levels were determined by electrophoretic mobility shift assay and Western blot, respectively.
Aspirin significantly inhibited cell proliferation and induced apoptosis at concentrations of 1, 4, 8 mmol/L. Aspirin dose-dependently decreased the levels of COX-2 mRNA, COX-2 protein and nuclear NF-kappaB protein and increased the cytoplasmic IkappaB protein.
We conclude that aspirin inhibits the proliferation of, and induced apoptosis in, the cultured TE-13 SCC cell line. These changes correlate with a reduction in COX-2 mRNA and protein expression, prostaglandin synthesis, an inhibition of NF-kappaB nuclear translocation, and an increase in cytoplasmic IkappaB. These results support the further investigation of the cyclooxygenase pathway in investigating the potential of aspirin and similar drugs in cancer prevention and therapy.
阿司匹林在预防或治疗食管癌方面具有潜力,食管癌是全球第七大常见癌症,但其作用机制仍不明确。
用不同浓度或不同时间的阿司匹林培养食管鳞状细胞癌细胞系TE-13。通过MTT比色法和流式细胞术检测细胞增殖和凋亡情况。用RT-PCR检测COX-2 mRNA的表达,用蛋白质印迹分析检测COX-2蛋白水平。分别通过电泳迁移率变动分析和蛋白质印迹法测定核NF-κB和细胞质IκB蛋白水平。
阿司匹林在1、4、8 mmol/L浓度时显著抑制细胞增殖并诱导凋亡。阿司匹林剂量依赖性地降低COX-2 mRNA、COX-2蛋白和核NF-κB蛋白水平,并增加细胞质IκB蛋白水平。
我们得出结论,阿司匹林抑制培养的TE-13鳞状细胞癌细胞系的增殖并诱导其凋亡。这些变化与COX-2 mRNA和蛋白表达的降低、前列腺素合成的减少、NF-κB核转位的抑制以及细胞质IκB的增加相关。这些结果支持在研究阿司匹林及类似药物在癌症预防和治疗中的潜力时进一步研究环氧化酶途径。