乙酰水杨酸对环氧合酶-2阴性结肠癌细胞增殖、凋亡及侵袭的影响。
The effects of acetylsalicylic acid on proliferation, apoptosis, and invasion of cyclooxygenase-2 negative colon cancer cells.
作者信息
Yu H-G, Huang J-A, Yang Y-N, Huang H, Luo H-S, Yu J-P, Meier J J, Schrader H, Bastian A, Schmidt W E, Schmitz F
机构信息
Department of Gastroenterology, RenMin Hospital of Wuhan University, Wuhan, China, Ruhr-University Bochum, Bochum, Germany.
出版信息
Eur J Clin Invest. 2002 Nov;32(11):838-46. doi: 10.1046/j.1365-2362.2002.01080.x.
BACKGROUND
Acetylsalicylic acid (ASA, aspirin), the most common nonsteroidal anti-inflammatory drug (NSAID), has been shown to have a protective effect against the incidence and mortality of colorectal cancer. However, the mechanism of its anticancer function remains unclear. The aim of this study was to determine the effects of acetylsalicylic acid on proliferation, apoptosis, and invasion in human cyclooxygenase-2 (COX-2) negative colorectal cancer cell lines.
MATERIALS AND METHODS
After treatment with various concentrations of ASA, cell proliferation was measured in the human colon cancer cell line SW480. Apoptotic cells were identified by transmission electron microscopy, acridine orange staining, and flow cytometry. The invasive potential of SW480 cells was detected using an in vitro invasion assay. The production of carcinoembryonic antigen was measured by microparticle enzyme immunoassay. Expression of Bcl2, Bax, CD44v6, and nm23 were evaluated by immunocytochemistry.
RESULTS
ASA significantly inhibited the proliferation of SW480 cells and stimulated apoptosis. Production of carcinoembryonic antigen and the invasive potential of SW480 cells were also inhibited by ASA. After treatment with ASA, down-regulation of Bcl2 and CD44v6 expression and up-regulation of nm23 expression were observed in SW480 cells. No obvious effect of ASA was found on Bax expression.
CONCLUSION
Our findings reveal that ASA inhibits the proliferation and promotes apoptosis in the human colon cancer cell line SW480. Down-regulation of Bcl2 expression might represent a potential mechanism by which ASA induces apoptosis in this COX-2 negative colon cancer cell line. Our results also suggest that ASA decreases the invasive potential of these colon cancer cells. Decreased CEA content and CD44v6 expression and elevated nm23 expression may contribute to the effect of ASA on invasive potential of SW480 colon cancer cells.
背景
乙酰水杨酸（ASA，阿司匹林）是最常见的非甾体抗炎药（NSAID），已被证明对结直肠癌的发病率和死亡率具有保护作用。然而，其抗癌功能的机制仍不清楚。本研究的目的是确定乙酰水杨酸对人环氧化酶-2（COX-2）阴性结直肠癌细胞系增殖、凋亡和侵袭的影响。
材料与方法
用不同浓度的ASA处理后，在人结肠癌细胞系SW480中检测细胞增殖。通过透射电子显微镜、吖啶橙染色和流式细胞术鉴定凋亡细胞。使用体外侵袭试验检测SW480细胞的侵袭潜能。通过微粒体酶免疫测定法测量癌胚抗原的产生。通过免疫细胞化学评估Bcl2、Bax、CD44v6和nm23的表达。
结果
ASA显著抑制SW480细胞的增殖并刺激凋亡。癌胚抗原的产生和SW480细胞的侵袭潜能也受到ASA的抑制。用ASA处理后，在SW480细胞中观察到Bcl2和CD44v6表达下调以及nm23表达上调。未发现ASA对Bax表达有明显影响。
结论
我们的研究结果表明，ASA抑制人结肠癌细胞系SW480的增殖并促进凋亡。Bcl2表达下调可能是ASA诱导该COX-2阴性结肠癌细胞系凋亡的潜在机制。我们的结果还表明，ASA降低了这些结肠癌细胞的侵袭潜能。癌胚抗原含量降低、CD44v6表达降低和nm23表达升高可能有助于ASA对SW480结肠癌细胞侵袭潜能的影响。
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