两种非甾体类抗炎药抑制结肠癌细胞增殖的机制

目的:研究选择性环氧合酶-2(COX-2)抑制剂尼美舒利与非选择性COX-2抑制剂舒林酸对结肠癌细胞株LOVO生长的影响,探讨其可能的机制。方法:采用四甲基偶氮唑蓝(MTT)比色法观察两药对结肠癌细胞增殖的抑制,流式细胞仪(FCM)分析其对细胞凋亡及细胞周期的影响,放免法分析其对PGE2的影响。结果:MTT显示尼美舒利、舒林酸均能抑制LOVO细胞的增殖,呈剂量和浓度依赖性。FCM显示两药均能促进细胞的凋亡,并能使G0/G1期细胞比例升高,S期细胞比例降低,与对照组相比均有显著性差异(P<0.05)。上清中PGE2表达水平呈剂量依赖性下调。结论:尼美舒利、舒林酸可抑制结肠癌细胞株LOVO的生长,促进其凋亡,其机制可能与其阻止细胞周期的进展,抑制COX-2的活性及PGE2的合成有关。

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibiting the proliferation of hum an colosectal cancer cells

Objective: To explore the mechanism that selective cyclooxygenase-2(COX-2) inhibitor Nimesulide and non-selective COX-2 inhibitor sulindac inhibited human colorectal cancer cells proliferation. Methods: MTT assay and flow cytometry(FCM) were used to determine the influence of Nimesulide and Sulindac on the proliferation and apoptosis of colorectal cancer cells.PGE2 was examined in the culture supernatant by radioimmunoassay. Results: Nimesulide and Sulindac inhibited proliferation of colorectal cancer cells in a dose-and time-dependent manner and significally increased the proportion of cells in the G0/G1 phase and decresed the proportion of cells in the S phase(P < 0.05). Both drugs reduced the release of PGE2 (P < 0.05). Conclusion: Nimesulide and Sulindac can inhibit proliferation and induce apoptosis in colorectal cancer cell lines,through inhibiting COX-2 activity and PGE2 synthasis and blocking the progession of cell cycle.