首页|2',4'-二羟基-3'-甲基-3-甲氧基查耳酮上调p21抑制人肝癌HepG2细胞的生长

2',4'-二羟基-3'-甲基-3-甲氧基查耳酮上调p21抑制人肝癌HepG2细胞的生长

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目的 探讨2',4'-二羟基-3'-甲基-3-甲氧基查耳酮(C20)对人肝癌HepG2细胞的体外抗肿瘤作用及其潜在的作用机制.方法 通过CCK-8法、集落形成实验、5-乙炔基-2'-脱氧尿苷(EdU)染色法检测C20对人肝癌HepG2细胞增殖的影响;通过彗星实验检测C20(10μmol·L-1)对HepG2细胞DNA损伤的影响;通过流式细胞术检测C20(5、10μmol·L-1)对HepG2细胞周期阻滞的影响;通过Hoechst染色和流式细胞术检测C20(5、10 μmol·L-1)对HepG2细胞凋亡的影响.借助Western blotting法检测C20(5、10 μmol·L-1)处理对HepG2细胞中与凋亡、DNA损伤、细胞周期阻滞相关蛋白表达水平的调控作用.结果 与对照组比较,C20显著抑制HepG2细胞的活力(P＜0.001),给药48 h的半数抑制浓度(IC50)为7.937 μmol·L-1;5 µmol·L-1 C20能够显著抑制HepG2细胞的集落形成能力(P＜0.01);EdU染色结果显示5、10 μmol·L-1的C20能够抑制人肝癌HepG2细胞的增殖能力;5、10 μmol·L-1的C20显著诱导HepG2细胞G2/M期阻滞(P＜0.001);5、10 μmol·L-1的C20显著促进HepG2细胞凋亡(P＜0.001),并显著上调Caspas-3、Caspase-9以及PARP的剪切水平(P＜0.01);10 μmol·L-1的C20能够诱导HepG2细胞发生DNA损伤,并且5、10 μmol·L-1的C20显著上调γH2AX、p21的蛋白水平(P＜0.01).结论 C20能够造成HepG2细胞发生DNA损伤,上调p21蛋白水平,导致细胞G2/M期阻滞,并进一步诱发凋亡,发挥体外抗肝癌作用.
2',4'-dihydroxy-3'-methyl-3-methoxychalcone inhibits growth of human hepatocellular carcinoma HepG2 cells through up-regulation of p21
Objective To investigate the in vitro antitumor effects of 2',4'-dihydroxy-3'-methyl-3-methoxychalcone(C20)on human hepatocellular carcinoma HepG2 cells and its potential mechanisms.Methods The effects of C20 on the proliferation of HepG2 cells were detected by CCK8 assay,colony formation assay,and 5-ethynyl-2'-deoxyuridine(EdU)staining assay.The effects of C20(10 μmol·L-1)on DNA damage of HepG2 cells were detected by comet assay.The effects of C20(5,10 μmol·L-1)on cell cycle of HepG2 cells were detected by flow cytometry.The effects of C20(5 and 10 μmol·L-1)on apoptosis of HepG2 cells were detected by Hoechst staining and flow cytometry.The effects of C20(5 and 10 μmol·L-1)on expression levels of proteins related to DNA damage,cell cycle,and apoptosis in HepG2 cells were detected by Western blotting.Results Compared with control group,C20 significantly inhibited the viability of HepG2 cells(P＜0.001),with a half-maximal inhibitory concentration(IC50)of 7.937 μmol·L-1 after 48 h of treatment;5 μmol·L-1 C20 significantly inhibited the colony-forming ability of HepG2 cells(P＜0.01);the EdU staining results showed that 5 and 10 μmol·L-1 of C20 could inhibit the proliferation of human hepatocellular carcinoma HepG2 cells;5 and 10 μmol·L-1 of C20 significantly induced G2/M phase arrest in HepG2 cells(P＜0.001);5 and 10 μmol·L-1 of C20 significantly promoted apoptosis in HepG2 cells(P＜0.001),and significantly upregulated the cleavage levels of Caspas-3,Caspase-9,and PARP(P＜0.01);10 μmol·L-1 of C20 could induce DNA damage in HepG2 cells,and 5 and 10 μmol·L-1 of C20 significantly upregulated the protein levels of γH2AX and p21(P＜0.01).Conclusion We speculate that C20 treatment can induce DNA damage and upregulate p21 expression in HepG2 cells,leading to G2/M arrest and further inducing apoptosis,which is partially responsible for anti-hepatocellular carcinoma activity of C20.

2',4'-dihydroxy-3'-methyl-3-methoxychalconehepatocellular carcinomaDNA damageG2/M arrestp21

王龙燕、张云封、王柱国、谭鹏、魏雪娇、李军、胡仲冬

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北京中医药大学中药学院,北京 100029

北京中医药大学北京中医药研究院中药现代研究中心,北京 100029

2',4'-二羟基-3'-甲基-3-甲氧基查耳酮 肝癌 DNA损伤 G2/M周期阻滞 p21

国家自然科学基金中央高校基本科研业务费专项北京中医药大学国家级人才精准培育计划国家中医药局青年岐黄学者支持项目

820740722023-JYB-JBQN-051JZPY202206

2024

10.7501/j.issn.1674-6376.2024.05.009

药物评价研究
天津药物研究院 中国药学会

药物评价研究

CSTPCD北大核心
影响因子：1.199
ISSN：1674-6376
年,卷(期)：2024.47(5)