棉籽酚诱导结肠癌细胞系凋亡的作用

Effects of gossypol in inducing apoptosis of human colon cancer cell lines

研究棉籽酚gossypol对结肠癌细胞的致凋亡作用及其方式。方法 :将不同浓度棉籽酚与结肠癌细胞株HT2 9和Lovo作用 ,采用集落形成法检测细胞经棉籽酚处理后的细胞存活曲线 ,通过荧光显微镜观察用药后细胞周期时相改变。结果 :HT2 9和Lovo经棉籽酚处理后增殖能力降低 ,2种细胞均显示明显凋亡征象 ,表现典型DNA梯 ,2种细胞均于用药后 2 4与 48h出现凋亡峰 (亚G1峰 ) ,并随药物浓度和用药时间增加而增加。细胞周期分布无明显变化。结论 :棉籽酚在体外能诱导结肠癌细胞发生G1期凋亡 ,抑制细胞增殖 ,是一种具有潜在抗肿瘤作用的化疗药 。

Purpose:To study the mode of action of gossypol which is a natural extract from the cotton plants on human coloncancer cell lines. Methods:Colon cancer cells HT29 and Lovo treated with various concentrations of gossypol were assessed. Surviving curves were obtained by colony forming assay. DNA gel electrophoresis and cell morphology study were used to observe evidenceof apoptosis. Cell cycle analysis was done by flow cytometry. Results:Cell proliferation of both HT29 and Lovo were decreased. Apoptotic DNA fragmentation were observed at 8 hours and 24 hours after drug teatment at 1 μmol/L,2 5 μmol/L,5 μmol/L on agarose gel electrophoresis. Cell morphology under ultraviolet fluorescence microscopy showed appearance of apoptotic bodies. Cell cycle analysis did not show any cell cycle distribution alteration. Both cell lines showed apoptotic peaks(subG1)at 24 hours and 48 hours after drug exposure, implying G1 apoptotic death to be dose and time dependent. Conclusions:Cossypol induces apoptosis and decreases cell proliferation in human colon cancer cell lines at low doses,suggesting that gossypol might be a potential alternative of chemotherapy agent for colon cancer.