[1]张一楠,任彩佩,吴亚俐,等.白藜芦醇通过调节铁死亡通路抑制小鼠溃疡性结肠炎相关性结肠癌实验研究[J].陕西医学杂志,2023,52(6):671-675,682.[doi:DOI:10.3969/j.issn.1000-7377.2023.06.008]
　ZHANG Yinan,REN Caipei,WU Yali,et al.Resveratrol inhibits ulcerative colitis-associated colorectal cancer in mice by regulating ferroptosis pathway[J].,2023,52(6):671-675,682.[doi:DOI:10.3969/j.issn.1000-7377.2023.06.008]
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白藜芦醇通过调节铁死亡通路抑制小鼠溃疡性结肠炎相关性结肠癌实验研究
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
52
期数:
2023年6期
页码:
671-675,682
栏目:
基础研究
出版日期:
2023-06-05

文章信息/Info

Title:
Resveratrol inhibits ulcerative colitis-associated colorectal cancer in mice by regulating ferroptosis pathway
作者:
张一楠; 任彩佩; 吴亚俐; 张文琴; 崔香丽
(山西医科大学生理学系 山西医科大学细胞生理学教育部重点实验室,山西 太原 030001)
Author(s):
ZHANG Yinan; REN Caipei; WU Yali; ZHANG Wenqin; CUI Xiangli
(Department of Physiology,Shanxi Medical University,Taiyuan 030001,China)
关键词:
溃疡性结肠炎相关性结肠癌;  白藜芦醇;  铁死亡通路;  小鼠;  人结肠癌HCT 116细胞
Keywords:
Ulcerative colitis-associated colorectal cancer;  Resveratrol;  Ferroptosis pathway;  Mice;  Human colon cancer HCT 116 cells
分类号:
R 735.34
DOI:
DOI:10.3969/j.issn.1000-7377.2023.06.008
文献标志码:
A
摘要:
目的:观察白藜芦醇(Res)是否可通过调节铁死亡通路抑制小鼠溃疡性结肠炎相关性结肠癌(UCACC)。方法:①将28只C57BL/6小鼠随机分为Control组、氧化偶氮甲烷(AOM)组、AOM+葡聚糖硫酸钠盐(DSS)组、AOM+DSS+Res组。造模实验周期为70 d。AOM组、AOM+DSS组和AOM+DSS+Res组第1天注射1次AOM。从造模第2周开始AOM+DSS组和AOM+DSS+Res组饮用含DSS水,第3周更换为无菌水,第4周换为含DSS水,以此循环到造模实验周期结束。Control组和AOM组饮用无菌水,AOM+DSS+Res组每周给予Res灌胃。造模结束后处死小鼠,取小鼠结肠组织,HE染色后观察小鼠结肠组织病理改变。分别采用免疫组织化学法(IHC)和Western blot 检测小鼠结肠组织谷胱甘肽过氧化物酶4(GPX4)、长链脂酰辅酶A合成酶4(ACSL4)、铁蛋白重链(FTH)、P53蛋白的表达。②将人结肠癌HCT 116细胞分为空白对照组及4、8、16 μg/ml Res组。用不同浓度(4、8、16 μg/ml)Res处理HCT 116细胞。收集处理的细胞后,采用CCK-8实验检测细胞增殖活性,采用Western blot检测细胞GPX4、ACSL4、FTH蛋白的表达。结果:①HE染色结果显示小鼠UCACC模型建模成功,Res可明显抑制AOM+DSS诱导的小鼠UCACC形成。IHC染色结果显示,与Control组比较,AOM组FTH蛋白表达下降; AOM+DSS组GPX4和FTH蛋白表达明显上升,ACSL4和P53蛋白表达明显下降(均P<0.05)。与AOM+DSS组比较,AOM+DSS+Res组GPX4和FTH蛋白表达下降,ACSL4和P53蛋白表达明显上升(均P<0.05)。Western blot检测结果显示,与Control组比较,AOM组GPX4、FTH蛋白表达下降,ACSL4表达上升; AOM+DSS组GPX4和FTH蛋白表达上升,ACSL4和P53蛋白表达下降(均P<0.05)。与AOM+DSS组比较,AOM+DSS+Res组GPX4和FTH蛋白表达下降,ACSL4和P53蛋白表达上升(均P<0.05)。②CCK-8实验结果显示,8、16 μg/ml Res组细胞存活率低于空白对照组(均P<0.05)。Western blot检测结果显示,与空白对照组比较,4、8、16 μg/ml Res组细胞GPX4和FTH蛋白表达下降,ACSL4蛋白表达上升(均P<0.05)。结论:Res可以通过调控细胞铁死亡通路抑制UCACC。
Abstract:
Objective:To investigate whether resveratrol(Res)can inhibit ulcerative colitis-associated colorectal cancer(UCACC)in mice by regulating ferroptosis pathway.Methods:①Twenty-eight C57BL/6 mice were randomly divided into Control group,azoxymethane(AOM)group,AOM+dextran sulfate sodium(DSS)group,and AOM+DSS+Res group.The period of modeling experiment was 70 days.AOM was injected once on the first day in AOM group,AOM+DSS group and AOM+DSS+Res group.The AOM+DSS group and AOM+DSS+Res group drank DSS-containing water from the second week of modeling,sterile water was replaced at the third week,and DSS-containing water was replaced at the fourth week,and this cycle was continued until the end of modeling.The Control and AOM groups were given sterile water,and the AOM+DSS+Res group was given Res by gavage every week.At the end of modeling,the mice were sacrificed,and the colon tissues of the mice were collected,and the pathological changes of the colon tissues of the mice were observed after HE staining.The protein expressions of glutathione peroxidase 4(GPX4),acyl-CoA synthetase long chain family member 4(ACSL4),ferritin heavy chain(FTH)and P53 in colon tissue of mice were detected by immunohistochemistry(IHC)and Western blot,respectively.②Human colon cancer HCT 116 cells were divided into blank control group and 4,8,16 μg/ml Res groups.HCT 116 cells were treated with Res at different concentrations(4,8,16 μg/ml),then the cells were collected,the cell proliferation activity was detected by CCK-8 test,and the protein expressions of GPX4,ACSL4 and FTH in cells were detected by Western blot.Results:①HE staining showed that the UCACC model was successfully established,and Res significantly inhibited the formation of UCACC in mice induced by AOM+DSS.IHC staining showed that compared with the Control group,the expression of FTH protein in the AOM group decreased; the protein expressions of GPX4 and FTH were significantly increased,while the protein expressions of ACSL4 and P53 were significantly decreased in the AOM+DSS group(all P<0.05).Compared with the AOM+DSS group,the protein expressions of GPX4 and FTH were decreased,while the protein expressions of ACSL4 and P53 were increased in the AOM+DSS+Res group(all P<0.05).Western blot results showed that compared with the Control group,the protein expressions of GPX4 and FTH in the AOM group decreased,and the protein expression of ACSL4 increased; the protein expressions of GPX4 and FTH increased and the protein expressions of ACSL4 and P53 decreased in the AOM+DSS group(all P<0.05).Compared with the AOM+DSS group,the protein expressions of GPX4 and FTH were decreased,and the protein expressions of ACSL4 and P53 were increased in the AOM+DSS+Res group(all P<0.05).②CCK-8 test results showed that the cell viability of 8 and 16 μg/ml Res groups was lower than that of the blank control group(all P<0.05).Western blot results showed that compared with the blank control group,the protein expressions of GPX4 and FTH were decreased,and the protein expression of ACSL4 was increased in the 4,8 and 16 μg/ml Res groups(all P<0.05).Conclusion:Res can inhibit UCACC by regulating the ferroptosis pathway.

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备注/Memo

备注/Memo:
基金项目:山西省自然科学基金资助项目(201801D121311); 山西省“1331工程”重点学科建设计划项目(1331KSC)
更新日期/Last Update: 2023-06-05