5-ARs抑制HCT116侵袭、转移机制的相关研究  

Study on the mechanism of 5-ARs inhibiting HCT116 invasion and metastasis

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作  者:李恒[1] 马硕 冯晓楠 董欣宇 宋伟[1] 李海[1] 杨春[1] LI Heng;MA Shuo;FENG Xiaonan;DONG Xinyu;SONG Wei;LI Hai;YANG Chun(Department of Colorectal Surgery,General Hospital of Ningxia Medical University,Yinchuan 750004,China;Department of Nephrology,General Hospital of Ningxia Medical University,Yinchuan 750004,China)

机构地区:[1]宁夏医科大学总医院结直肠外科,宁夏银川750004 [2]宁夏医科大学总医院肾脏内科,宁夏银川750004

出  处:《宁夏医学杂志》2023年第1期8-11,共4页Ningxia Medical Journal

基  金:宁夏自然科学基金项目(2019AAC03199);宁夏医科大学校级课题(202007)。

摘  要:目的分析5-烷基间苯二酚(5-ARs)影响人结直肠癌细胞系(HCT116)的侵袭转移能力,探讨其潜在的作用机制。方法应用5-ARs对HCT116细胞进行干预诱导,CCK-8法测定不同浓度梯度的5-ARs对人结直肠癌细胞系HCT116的抑制率,计算适宜的干预浓度;利用倒置显微镜观察5-ARs对HCT116细胞干预后形态的变化,Western-blot检测5-ARs诱导HCT116后氧化相关蛋白(Nrf2)和谷胱甘肽代谢相关蛋白(GCLC和GCLM)的变化。结果通过设置不同的浓度梯度,5-ARs最适宜的干预浓度为33.01μg/mL;5-ARs可显著抑制人结直肠癌细胞HCT116侵袭和转移能力(P<0.05),并抑制GCLC和GCLM的表达,及在胞浆和核内调节Nrf2的表达,从而调控HCT116细胞的凋亡(P<0.05)。结论5-ARs可抑制人结直肠癌细胞系HCT116的侵袭、转移。5-ARs通过抑制肿瘤细胞的GCLM和GCLC蛋白的表达,分别调控肿瘤细胞胞浆和胞核Nrf2蛋白的差异化表达,其可能参与肿瘤细胞的谷胱甘肽代谢机制和细胞凋亡机制。Objective To analyze the effect of 5-alkyl resorcinol(5-ARs)on the invasion and metastasis of human colorectal cancer cell line(HCT116)and explore its potential mechanism.Methods HCT116 cells were induced by 5-ARs.CCK-8 method was used to determine the inhibition rate of 5-ARs with different concentration gradients on human colorectal cancer cell line HCT116,and calculated the appropriate intervention concentration;Inverted microscope was used to observe the morphological changes of HCT116 cells after intervention by 5-ARs.Western blot was used to detect the changes of oxidation related protein(Nrf2)and glutathione metabolism related protein(GCLC and GCLM)after 5-ARs induced HCT116 cells.Results By setting different concentration gradients,the optimal intervention concentration of 5-ARs was 33.01μg/mL;5-ARs inhibited the invasion and metastasis of human colorectal cancer cells HCT116(P<0.05),and inhibited the expression of GCLC and GCLM,and different regulation of Nrf2 expression in cytoplasm and nucleus,thereby it regulated the apoptosis of HCT116 cells(P<0.05).Conclusions 5-ARs can inhibit the invasion and metastasis of human colorectal cancer cell line HCT116,and the mechanism of action may be related to inhibiting the expression of GCLC and GCLM proteins to inhibit the glutathione metabolic pathway,and regulating the expression of Nrf2 to inhibit cell oxidation and then regulate the apoptosis pathway.

关 键 词:5-烷基间苯二酚 细胞凋亡 结直肠肿瘤 

分 类 号:R735.34[医药卫生—肿瘤]

 

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