gms | German Medical Science

Introduction: Augmenter of Liver Regeneration (ALR) is a protein that carries out cytokine and enzymatic functions. Recently, it has been shown that ALR is expressed in hepatocellular carcinomas to a different extent depending on the grade and invasiveness. Since ALR has been shown to promote liver regeneration and protect against apoptosis caused by a variety of harmful substances, this study aims to determine if ALR protects hepatocellular carcinoma cells against treatment with the chemotherapeutic agents and if so, the signalling pathways through which ALR exerts its protective effect.

Material and methods: BEL7402, a hepatocellular carcinoma cell line, was transfected with an empty vector or an ALR-containing vector. Control and ALR-overexpressing cell lines were untreated or treated with 15 μg/ml cisplatin over a 24 h time-course. At 3, 6 and 24 h, caspase activities and contents of proteins in the AKT and ERK signalling pathways were determined.

Results: Compared to the empty vector-transfected BEL7402 cells, cells transfected with ALR had a significant reduction in caspase 3 activity at 24 h by 1.6-fold when treated with cisplatin. This protection appears to be mediated over a time-course by an up-regulation in phospho-AKT, but not phospho-ERK.

Conclusion: Overexpression of ALR in BEL7402, results in protection against apoptosis caused by cisplatin. This protection could be mediated through the AKT pathway. Thus, cisplatin may be a good treatment strategy for hepatocellular carcinomas with low ALR expression, but may not be suitable for tumours with high ALR expression. In future studies, it would be important to determine if there are other chemotherapeutic agents that ALR does not protect against that can be used as a more effective strategy or to determine if cisplatin treatment should be done in parallel with an AKT inhibitor for increased efficacy.