亚油酸/二十二碳六稀酸对胃癌细胞凋亡作用

Effect leinoleic acid/docosahexaenoic acid on apoptosis of human gastric cancer cells

目的探讨不同比例亚油酸(LA)/二十二碳六稀酸(DHA)对人胃癌细胞株MKN-45的抑制作用。方法采用均匀设计法初筛出LA/DHA抑制MKN-45增殖的较佳比例,采用随机区组法确定促进胃癌细胞凋亡的最佳比例;采用LA/DHA最佳比例混合脂肪酸干预MKN-45裸小鼠移植模型6周,观察裸鼠肿瘤重量、肿瘤体积变化及毒副反应情况;肿瘤组织HE染色观察肿瘤细胞形态学改变。结果经均匀设计和随机区组筛选,LA/DHA比例为1∶3时,浓度为40∶120μmol/L时,对肿瘤细胞的抑制效果最佳(P<0.05);与对照组比较,1∶3 LA/DHA混合脂肪酸高剂量组瘤体抑制率为21.97%,瘤重的抑制率为18.09%,差异有统计学意义(P<0.05);肿瘤组织病理切片显示,高剂量组和抗癌药物阳性对照组的肿瘤组织中出现不同程度坏死;高剂量组毒副反应不明显。结论LA/DHA比例为1∶3可诱导人胃癌MKN-45细胞凋亡;LA/DHA高剂量组有一定抑瘤作用,并且无明显毒副反应。

Objective To explore the effects of different constituent ratio leinoleic acid （LA）/docosahexaenoic acid （DHA） on apoptosis of human gastric cancer cell line MKN-45. Methods With uniform design, the better constituent ratio for the inhibition of MKN-45 cell was scrceend. Then the best ratio was determined with randomized block design. The tumor volume, side-effect, and tumor weigh of tumor-beating nude mice after treatment were observed. The morphological changes of tumor tissue were assessed by HE staining. Results The LA/DHA constituent ratio of 1：3 showed maximum inhibition of the tumor cells. Six weeks after high concentration treatment, the mean tumor volume decreased by 21.97% and the mean tumor weigh by 18.09% with statistical significance compared with that of control group（P 〈0. 05）. The toxicity of the treatment was not obvious. Microscopic examination showed that there were massive areas of cytoclasis and apoptosis in the tumor tissue of the high concentration group and 5-FU group. Conclusion The 1：3 constituent ratio of LA/DHA could induce the apoptosis of human gastric cancer cell line MKN-45. The high concentration of 1：3 constituent ratio treatment could also inhibit tumor in vivo without significant side-effect.