摘要
目的:探讨救必应的有效成分长梗冬青苷在结肠炎相关性结直肠癌(Colitis-Assosiated Colorectal Cancer,CAC)小鼠模型中的干预机制。方法:采用氧化偶氮甲烷(AOM)/葡聚糖硫酸钠(DSS)方法建立C57BL/6小鼠CAC模型,检测结肠组织中miR-29a、TET3及STAT3基因蛋白的表达。体外实验采用人结肠癌细胞株HCT116,检测长梗冬青苷对其生长的抑制作用;检测长梗冬青苷对高表达miR-29a后HCT116中TET3蛋白的表达变化。结果:模型小鼠出现结肠黏膜中、重度异型增生并且伴随着大量炎细胞的浸润;结肠组织中miR-29a的表达水平显著上调;STAT3蛋白表达明显升高,TET3蛋白的表达下降。长梗冬青苷25 mg/kg干预后可显著下调miR-29a表达水平;下调结肠组织STAT3的表达并上调TET3蛋白的表达。体外结果表明,长梗冬青苷10μmol/L 12h、24h和48h均可抑制HCT116细胞增殖;且逆转HCT116细胞中miR-29a precursor引起的TET3蛋白表达的下降。结论:长梗冬青苷可以抑制CAC小鼠结肠miR-29a表达,上调miR-29a下游靶蛋白TET3的表达,同时抑制STAT3蛋白表达,可能是其干预CAC模型中结肠炎-癌病理发展的部分机制。
To study the intervention mechanism of Pedunculoside(PDC),an effective component of JiuBiYing,in colitis-associated colorectal cancer(CAC)mice model.Methods:The CAC model of C57 BL/6 mice was established by AOM/DSS method.The gene protein expression of MiR-29 a,TET3 and STAT3 in the colon tissue was detected.In vitro,human colon cancer cell line HCT116 was used to detect the inhibitory effect of PDC on its growth and the expression of TET3 protein in HCT116 after the high expression of miR-29 a.Results:Moderate to severe dysplasia of colonic mucosa was observed in model mice,accompanied by infiltration of a large number of inflammatory cells.The expression of miR-29 a in colonic tissues was significantly increased,the expression of STAT3 protein was significantly increased,and the expression of TET3 protein was decreased.After PDC intervention,the expression of miR-29 a was significantly down-regulated,the expression of STAT3 in colon tissues was decreased and the expression of TET3 protein was increased.In vitro results showed that PDC(10μmol/L)inhibited the proliferation of HCT116 cells at 12,24 and 48 hours,and reversed the decrease of TET3 protein expression induced by miR-29 a precursor in HCT116 cells.Conclusion:Pedunculoside has the effect on colitis associated colorectal cancer,its mechanism may be related to inhibiting the miR-29 a level,up regulating the target gene TET3 and inhibiting the expression of STAT3.
作者
陈曦
程博
宋宁
巫燕莉
李燕舞
Chen Xi;Cheng Bo;Song Ning;Wu Yanli;Li Yanwu(Guangzhou University of Traditional Chinese Medicine,Guangzhou 510000;Henan University of Traditional Chinese Medicine,Zhengzhou 450000)
出处
《中药药理与临床》
CAS
CSCD
北大核心
2019年第5期39-42,共4页
Pharmacology and Clinics of Chinese Materia Medica
基金
广东省教育厅特色创新类项目(2018KTSCX043)
“广州中医药大学薪火计划”项目(A1-AFD015141Z0234)
