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目的 评价 5 脂质加氧酶 ( 5 LOX)代谢途径在胃癌中的作用及 5 LOX抑制剂对胃癌细胞凋亡的影响。方法 用LOX抑制剂 NDGA ,处理表达 5 LOXmRNA及蛋白的胃癌细胞系AGS和不表达相应物质的胃癌细胞系MKN2 8。MTT法检测细胞增殖情况。吖啶橙染色、DNA琼脂糖凝胶电泳和流式细胞术观察细胞凋亡。结果 NDGA对AGS增殖的抑制及诱导其凋亡呈时间和剂量依耐性 ,而对MKN2 8细胞系无影响。 5 LOX的代谢产物 LTD4可抑制NDGA诱导的细胞凋亡。结论 NDGA诱导AGS细胞系的凋亡依耐于 5 LOX的表达 ;选择性阻断 5 LOX代谢途径的制剂可用于胃癌的化学阻断。
Objective To evaluate the role of lipoxygenase (5 LOX) metabolic pathway in gastric cancer and the effect of 5 LOX inhibitors on gastric cancer cell apoptosis. Methods The gastric cancer cell line AGS expressing 5 LOX mRNA and protein and the gastric cancer cell line MKN28 expressing no corresponding substance were treated with the LOX inhibitor NDGA. MTT assay detected cell proliferation. Acridine orange staining, DNA agarose gel electrophoresis and flow cytometry were used to observe apoptosis. RESULTS: NDGA showed time and dose-dependent resistance to AGS proliferation and induction of apoptosis, but had no effect on MKN28 cell line. 5 LOX metabolite LTD4 can inhibit NDGA-induced apoptosis. Conclusion The apoptosis of AGS cell line induced by NDGA is dependent on the expression of 5 LOX, and the selective blockade of 5 LOX metabolic pathway can be used for the chemical blocking of gastric cancer.