浅蓝菌素诱发人结肠癌细胞凋亡的实验研究

An experimental study on cerulenin induced apoptosis of human colonic cancer cells

目的 探讨脂肪酸合酶抑制剂———浅蓝菌素能否阻遏人结肠癌细胞增殖与诱发凋亡。方法 采用人结肠癌细胞系LoVo ,应用细胞形态学观察 ,噻唑蓝法 (MTT法 ) ,片断DNA琼脂糖凝胶电泳及流式细胞仪等方法进行检测和观察。结果 LoVo细胞在浅蓝菌素作用下 ,细胞增殖被阻遏 ,并呈现剂量效应关系 ,浅蓝菌素浓度 10 -9～ 10 -5mol/L增殖抑制率由 ( 2 1.0± 15 .9) %到 ( 96 .3± 2 7) %(P <0 .0 5或 0 .0 1)。同时诱发细胞发生凋亡。凋亡细胞表现为细胞固缩 ,核染色质凝聚、边集或断裂。细胞DNA裂解片段呈典型的“阶梯状”排列的条带 ,流式细胞仪显示“凋亡”峰 ,细胞周期分析浅蓝菌素能阻滞肿瘤细胞从S期进入G2 M期 ,并诱导其细胞凋亡。浅蓝菌素对人成纤维细胞增殖无明显影响。结论 脂肪酸合酶抑制剂可能通过抑制LoVo细胞内源性脂肪酸合成 。

Objective To investigate whether cerulenin could induce apoptosis and suppress the proliferation of human colonic cancer cells. Methods Cell morphology, microculture tetrazolium assay (MTT),agarose gel electrophoresis and flow cytometry assays were performed to indentify the inhibitory effect on cell proliferation and the induction of apoptosis in human colonic cancer cells (LoVo). Results Cerulenin was able to induce LoVo cells death via apoptosis. Cerulenin also inhibited the proliferation of LoVo cells in vitro and was dosedependent. Nuclear DNA of apoptotic cells displayed ladder bands characteristic of internucleosomal DNA fragmentation and apoptotic peak. The inhibitory effect of cerulenin on proliferation of LoVo cells was associated with cell cycle arrest from S to G 2M phase transition and with induction of apoptosis. In contrast, cerulenin could not affect the proliferation of human fibroblasts in vitro. Conclusion The fatty acid synthase inhibitor, cerulenin, enables to induce cell apoptosis and to suppress the growth of human colonic cancer cells by inhibition of the synthesized fatty acids endogenously in the cancer cells.