李怡, 李国艳, 程丽, 李格格, 李艾铭, 杨子琰, 崔红梅. MitoCur-1通过靶向抑制泛素特异性蛋白酶14对肝细胞癌的影响[J]. 职业卫生与应急救援, 2025, 43(2): 239-245, 258. DOI: 10.16369/j.oher.issn.1007-1326.2025.240568
引用本文: 李怡, 李国艳, 程丽, 李格格, 李艾铭, 杨子琰, 崔红梅. MitoCur-1通过靶向抑制泛素特异性蛋白酶14对肝细胞癌的影响[J]. 职业卫生与应急救援, 2025, 43(2): 239-245, 258. DOI: 10.16369/j.oher.issn.1007-1326.2025.240568
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LI Yi, LI Guoyan, CHENG Li, LI Gege, LI Aiming, YANG Ziyan, CUI Hongmei. Effect of MitoCur-1 on development of hepatocellular carcinoma by targeting inhibition of ubiquitin-specific protease 14[J]. Occupational Health and Emergency Rescue, 2025, 43(2): 239-245, 258. DOI: 10.16369/j.oher.issn.1007-1326.2025.240568
Citation: LI Yi, LI Guoyan, CHENG Li, LI Gege, LI Aiming, YANG Ziyan, CUI Hongmei. Effect of MitoCur-1 on development of hepatocellular carcinoma by targeting inhibition of ubiquitin-specific protease 14[J]. Occupational Health and Emergency Rescue, 2025, 43(2): 239-245, 258. DOI: 10.16369/j.oher.issn.1007-1326.2025.240568
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MitoCur-1通过靶向抑制泛素特异性蛋白酶14对肝细胞癌的影响

Effect of MitoCur-1 on development of hepatocellular carcinoma by targeting inhibition of ubiquitin-specific protease 14

    摘要
  • 摘要:
    目的 探究MitoCur-1通过抑制泛素特异性蛋白酶14（USP14）对肝细胞癌增殖、迁移的影响，为MitoCur-1的抗肿瘤作用提供理论依据。
    方法 首先，体外培养HepG2细胞，应用CCK-8实验和克隆形成实验检测MitoCur-1对细胞增殖能力的影响；应用划痕实验检测MitoCur-1对细胞迁移能力的影响；应用实时荧光定量PCR、蛋白质印迹法检测MitoCur-1作用于HepG2后细胞内USP14的mRNA和蛋白表达水平的变化；放线菌酮（CHX）实验检测MitoCur-1对蛋白半衰期的影响；其次，构建动物模型，应用苏木精-伊红染色（HE）和免疫组织化学（IHC）法，检测MitoCur-1在体内的抗肿瘤效应。
    结果 HepG2的细胞活力随MitoCur-1浓度的升高而降低，细胞的IC50为3.62 μmol/L。与对照组相比，0.2、0.4、0.8 μmol/L MitoCur-1处理后，HepG2细胞的克隆形成能力均有下降（均P < 0.05）。1、2、4 μmol/L的MitoCur-1处理48 h，HepG2细胞迁移能力均下降（均P < 0.05）。与对照组相比，1、2、4 μmol/LMitoCur-1处理HepG2细胞24 h，USP14的mRNA和蛋白表达水平均下降（均P < 0.05）。CHX实验结果提示，MitoCur-1缩短了USP14的蛋白半衰期（P < 0.05）。体内实验显示，15 mg/kg（以体重计）MitoCur-1给药组小鼠肿瘤体积增长速度减缓，肿瘤体积明显低于对照组（P < 0.05），但小鼠体重总体上增长，与对照组差异无统计学意义（P >0.05）。
    结论 MitoCur-1能抑制USP14的表达，降低HepG2细胞的增殖、迁移能力，诱导肿瘤细胞发生凋亡，促进自噬，抑制肝细胞癌的发展。

     

    Abstract:
    Objective To investigate the effects of MitoCur-1 on the proliferation and migration of hepatocellular carcinoma through the inhibition of ubiquitin-specific protease 14 (USP14), providing a theoretical basis for the antitumor activity of MitoCur-1.
    Methods HepG2 cells were cultured in vitro, and CCK-8 assays and colony formation assays were used to assess the effects of MitoCur-1 on cell proliferation. The scratch assay was employed to evaluate the impact of MitoCur-1 on cell migration. real-time quantitative PCR (RT-qPCR) and Western blot were performed to detect changes in both USP14 mRNA and protein expression levels in HepG2 cells after treatment with MitoCur-1. The CHX assay was conducted to examine the effect of MitoCur-1 on protein half-life. An animal model was established, and hematoxylin and eosin (HE) staining along with immunohistochemistry (IHC) were used to analyze the in vivo antitumor effects of MitoCur-1.
    Results The cell viability of HepG2 cells decreased with increasing concentrations of MitoCur-1, with an IC50 of 3.62 μmol/L. Compared to the control group, MitoCur-1 at concentrations of 0.2, 0.4, and 0.8 μmol/L significantly reduced the colony formation ability of HepG2 cells (all P < 0.05). After 48 hours of treatment with 1, 2, and 4 μmol/L MitoCur-1, the migratory ability of HepG2 cells was diminished (all P < 0.05). Additionally, treatment with 1, 2, and 4 μmol/L MitoCur-1 for 24 hours led to decreased mRNA and protein expression levels of USP14 in HepG2 cells compared to the control group (all P < 0.05). CHX assay results indicated that MitoCur-1 reduced the protein half-life of USP14 (P < 0.05). The experiments in vivo showed that the growth rate of tumor volume was slowed in the 15 mg/kg (in body weight) MitoCur-1 group of mice, resulting in a significantly lower tumor volume than that of the control group (P < 0.05). However, there was no statistically significant difference in the overall weight gain of mice between the treated and control groups (P > 0.05).
    Conclusions MitoCur-1 treatments inhibited the expression of USP14, reduced the proliferation and migratory capabilities of HepG2 cells, induced apoptosis, promoted autophagy, and suppressed the development of hepatocellular carcinoma.

     

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