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

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 in vitro and in vivo models to investigate the effects of ALR in HCC as well as its mechanism of action. We produced and characterized a human ALRspecific monoclonal antibody (mAb) and investigated the effects of the mAb in HCC cells. Results: The purified ALRspecific mAb matched the predicted molecular weight of IgG heavy and light chains. Thereafter, we used the ALRspecific 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.

Loss of nephric augmenter of liver regeneration facilitates acute kidney injury via ACSL4‐mediated ferroptosis

“…We speculate that feedback mechanisms caused by high ROS stress may be involved in AKI. In addition, several reports demonstrate that ALR is a secreted cytokine 43,44 . To further elucidate the protective role of ALR on ferroptosis in I/R injury‐induced AKI, we used a kidney‐specific ALR knockout mouse model.…”

“…In addition, several reports demonstrate that ALR is a secreted cytokine. 43 , 44 To further elucidate the protective role of ALR on ferroptosis in I/R injury‐induced AKI, we used a kidney‐specific ALR knockout mouse model. We also established an AKI mouse model by inducing bilateral ischemia for 22 min 45 and reperfusion for 24 h. Knockout of ALR causes serious pathological damage, and the mortality rate of ALR KO mice was approximately 50% (data not shown).…”

Upregulation of FAM134B inhibits endoplasmic reticulum stress‐related degradation protein expression and promotes hepatocellular carcinogenesis

“…Hepatocytes sustain hepatic functional equilibrium through regeneration and apoptosis. Imbalances between hepatocyte regeneration and apoptosis can spur excessive hepatocarcinoma cell proliferation and disruption of normal cellular growth control, eventually precipitating HCC formation 9,10 . Considerable abnormalities in angiogenesis are observed in HCC.…”

“…Imbalances between hepatocyte regeneration and apoptosis can spur excessive hepatocarcinoma cell proliferation and disruption of normal cellular growth control, eventually precipitating HCC formation. 9 , 10 Considerable abnormalities in angiogenesis are observed in HCC. Neovascularization differentiation and expansion within cancerous tissue constitute important mechanisms for HCC invasion and metastasis, providing abundant nourishment and oxygen to HCC cells.…”