黑树莓花青素联合奥沙利铂或喜树碱通过Akt信号通路协同增强结直肠癌化疗药物的治疗效果及作用机制研究

Black raspberry anthocyanins combined with oxaliplatin or camptothecin synergistically enhance therapeutic effect of colorectal cancer chemotherapy drugs and mechanism through Akt signaling pathway

目的探究黑树莓花青素联合奥沙利铂或喜树碱在结直肠癌细胞和氧化偶氮甲烷(azoxymethane,AOM)诱导的结直肠癌模型小鼠中的协同作用。方法结直肠癌细胞系SW480和Caco-2给予黑树莓花青素、奥沙利铂或喜树碱进行干预,AOM诱导的结直肠癌模型小鼠给予黑树莓花青素或奥沙利铂进行干预。采用MTT法检测黑树莓花青素联合奥沙利铂或喜树碱对结直肠癌细胞增殖的影响;采用Western blotting法检测结直肠癌细胞和小鼠肠上皮细胞中蛋白激酶B(protein kinase B,Akt)信号通路相关蛋白表达;采用苏木素-伊红(HE)染色检测小鼠结肠组织病理变化。结果黑树莓花青素与奥沙利铂或喜树碱联合使用可显著抑制SW480和Caco-2细胞的增殖(P<0.05、0.01、0.001);黑树莓花青素与奥沙利铂联合使用显著改善结直肠癌模型小鼠的状态,增加小鼠体质量,减少肠道肿瘤数量(P<0.01);黑树莓花青素可能通过下调Akt信号通路相关蛋白的表达进而增强化疗药物的治疗效果(P<0.01、0.001)。结论黑树莓花青素可以协同增加奥沙利铂或喜树碱的抗肿瘤作用。

Objective To explore the synergistic effect of black raspberry anthocyanins combined with oxaliplatin or camptothecin on colorectal cancer cells and azoxymethane(AOM)-induced colorectal cancer mouse model.Methods Colorectal cancer cell lines SW480 and Caco-2 were treated with black raspberry anthocyanins,oxaliplatin or camptothecin,and AOM-induced colorectal cancer model mice were treated with black raspberry anthocyanins or oxaliplatin.MTT assay was used to detect the effect of black raspberry anthocyanins combined with oxaliplatin or camptothecin on proliferation of colorectal cancer cells;Western blotting was used to detect protein kinase B(Akt)signaling pathway-related protein expression in colorectal cancer cells and mouse intestinal epithelial cells;Hematoxylin-eosin(HE)staining was used to detect the pathological changes of colon tissue in mice.Results The combined use of black raspberry anthocyanins and oxaliplatin or camptothecin could significantly inhibit the proliferation of SW480 and Caco-2 cells(P<0.05,0.01,0.001);The combined use of black raspberry anthocyanins and oxaliplatin significantly improved the state of colorectal cancer mouse model,increased the body weight of mice,and reduced the number of intestinal tumors(P<0.01);Black raspberry anthocyanins enhanced the therapeutic effect of chemotherapy drugs by down-regulating the expression of Akt signaling pathwayrelated proteins(P<0.01,0.001).Conclusion Black raspberry anthocyanins can synergistically increase the antitumor effect of oxaliplatin or camptothecin.