首页|Nodosin通过抑制mTOR通路和激活自噬诱导结直肠癌细胞凋亡

Nodosin通过抑制mTOR通路和激活自噬诱导结直肠癌细胞凋亡

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背景:结直肠癌是消化道常见的恶性肿瘤,现有的治疗方法和药物具有毒副反应大等缺点,因此迫切需要研发出高效低毒的新型治疗药物.目的:探讨Nodosin诱导结直肠癌细胞凋亡的机制.方法:体外培养结直肠癌细胞株SW480、HCT116,以0、5、10和20 µmol/L Nodosin处理细胞24 h,或以10 µmol/L Nodosin处理细胞0、12、24和48 h.以CCK-8法检测细胞活性,蛋白质印迹法检测PARP1、mTOR、p-mTOR、LC3BⅡ蛋白表达.SW480、HCT116细胞以5 mmol/L自噬抑制剂3-甲基腺嘌呤(3-MA)预处理4 h以后,与10 µmol/L Nodosin培养24 h,蛋白质印迹法检测PARP1、LC3BⅡ蛋白表达.结果:Nodosin能呈浓度依赖性和时间依赖性地抑制SW480、HCT116细胞活性,凋亡相关蛋白cleaved PARP1和自噬相关蛋白LC3BⅡ表达升高,p-mTOR表达受抑.自噬抑制剂3-MA预处理可抑制Nodosin诱导的凋亡相关蛋白cleaved PARP1和自噬相关蛋白LC3BⅡ表达.结论:Nodosin可通过抑制mTOR通路和激活自噬诱导结直肠癌细胞凋亡.
Nodosin Induces Apoptosis of Colorectal Cancer Cells by Inhibiting mTOR Pathway and Activating Autophagy
Background:Colorectal cancer is a common malignant tumor in the digestive tract.The existing treatment methods and drugs have disadvantages such as significant toxicity and side effects,so there is an urgent need to develop new drugs with high efficiency and low toxicity.Aims:To investigate the potential mechanism of Nodosin in inducing apoptosis of colorectal cancer cells.Methods:Colorectal cancer cell lines SW480 and HCT116 were cultured with 0,5,10 and 20 µmol/L Nodosin for 24 hours,or cultured with 10 µmol/L Nodosin for 0,12,24 and 48 hours.The cell viability was measured by CCK-8 assay,and the protein expressions of PARP1,mTOR,p-mTOR and LC3BⅡ were detected by Western blotting.After pretreated with the autophagy inhibitor 3-methyladenine(3-MA)5 mmol/L for 4 hours,SW480 and HCT116 cells were cultured with 10 µmol/L Nodosin for 24 hours.The protein expressions of PARP1 and LC3BⅡ were detected by Western blotting.Results:Nodosin could decrease the cell viability of SW480 and HCT116 cells in a dose-and time-dependent manner,increase the expressions of apoptosis-related protein cleaved PARP1 and autophagy-related protein LC3BⅡ,and inhibit the protein expression of p-mTOR.Pretreatment of the autophagy inhibitor 3-MA could inhibit the expressions of apoptosis-related protein cleaved PARP1 and autophagy-related protein LC3BⅡ induced by Nodosin.Conclusions:Nodosin can induce apoptosis of colorectal cancer cells by inhibiting mTOR pathway and activating autophagy.

NodosinAutophagyColorectal NeoplasmsApoptosis

张虹、蔡莎莎、解春琴、喻长法、方涵

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浙江省台州市第一人民医院检验科(318020)

Nodosin 自噬 结直肠肿瘤 细胞凋亡

2024

胃肠病学
上海交通大学医学院附属仁济医院

胃肠病学

CSTPCD
影响因子:1.217
ISSN:1008-7125
年,卷(期):2024.29(5)