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肝再生增强因子单克隆抗体促进肝癌细胞凋亡

Augmenter of Liver Regeneration Monoclonal Antibody Promotes Apoptosis of Hepatocellular Carcinoma Cells.

作者信息

Huang Li-Li, Luo Fei-Yang, Huang Wen-Qi, Guo Hui, Liu Qi, Zhang Ling, Jin Ai-Shun, Sun Hang

机构信息

Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.

Department of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing, China.

出版信息

J Clin Transl Hepatol. 2023 Jun 28;11(3):605-613. doi: 10.14218/JCTH.2022.00346. Epub 2023 Jan 4.

Abstract

BACKGROUND AND AIMS

Hepatocellular carcinoma (HCC) is one of the most common types of cancer, often resulting in death. Augmenter of liver regeneration (ALR), a widely expressed multifunctional protein, has roles in liver disease. In our previous study, we reported that ALR knockdown inhibited cell proliferation and promoted cell death. However, there is no study on the roles of ALR in HCC.

METHODS

We used and models to investigate the effects of ALR in HCC as well as its mechanism of action. We produced and characterized a human ALR-specific monoclonal antibody (mAb) and investigated the effects of the mAb in HCC cells.

RESULTS

The purified ALR-specific mAb matched the predicted molecular weight of IgG heavy and light chains. Thereafter, we used the ALR-specific mAb as a therapeutic strategy to suppress tumor growth in nude mice. Additionally, we assessed the proliferation and viability of three HCC cell lines, Hep G2, Huh-7, and MHC97-H, treated with the ALR-specific mAb. Compared with controls, tumor growth was inhibited in mice treated with the ALR-specific mAb at 5 mg/kg, as shown by hematoxylin and eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling. Simultaneous treatment with the ALR-specific mAb and adriamycin promoted apoptosis, whereas treatment with the ALR-specific mAb alone inhibited cell proliferation.

CONCLUSIONS

The ALR-specific mAb might be a novel therapy for HCC by blocking extracellular ALR.

摘要

背景与目的

肝细胞癌(HCC)是最常见的癌症类型之一,常导致死亡。肝脏再生增强因子(ALR)是一种广泛表达的多功能蛋白,在肝脏疾病中发挥作用。在我们之前的研究中,我们报道ALR基因敲低可抑制细胞增殖并促进细胞死亡。然而,尚无关于ALR在HCC中作用的研究。

方法

我们使用[具体模型1]和[具体模型2]模型来研究ALR在HCC中的作用及其作用机制。我们制备并鉴定了一种人ALR特异性单克隆抗体(mAb),并研究了该mAb对HCC细胞的影响。

结果

纯化的ALR特异性mAb与预测的IgG重链和轻链分子量相匹配。此后,我们使用ALR特异性mAb作为一种治疗策略来抑制裸鼠肿瘤生长。此外,我们评估了用ALR特异性mAb处理的三种HCC细胞系Hep G2、Huh-7和MHC97-H的增殖和活力。苏木精和伊红染色及末端脱氧核苷酸转移酶dUTP缺口末端标记显示,与对照组相比,用5mg/kg的ALR特异性mAb处理的小鼠肿瘤生长受到抑制。ALR特异性mAb与阿霉素同时处理可促进细胞凋亡,而单独用ALR特异性mAb处理则抑制细胞增殖。

结论

ALR特异性mAb可能通过阻断细胞外ALR成为HCC的一种新疗法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd38/10037511/461182deeb3c/JCTH-11-605-g001.jpg

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