Cathepsin Inhibitor Suppresses the Growth of Ectopic Hepatocellular Carcinoma Tumors in Mouse Models
Year: 2026
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide The advanced stages of hepatocellular carcinoma (HCC) are challenging to treat because of the invasion of blood vessels by malignant cells, as well as underlying cirrhosis in most patients. Current chemotherapeutic approaches are hindered by limited efficacy, systemic toxicity, and drug resistance. Therefore, developing new chemotherapeutic agents that can be used alone or as part of a cocktail regimen could aid in the treatment of HCC patients. This study primarily focuses on a cathepsin inhibitor and its antiproliferative effects on HCC cell lines in vitro and in HCC tumor xenografts in mouse models. The results show that the inhibitor has significant antiproliferative effects on the Hep G2 and Hep 3B cell lines, with low micromolar CC 50 values. Furthermore, the compound inhibits both recombinant and endogenous cathepsin L and cathepsin S in a time-dependent manner. In mice, significant reductions in the growth of subcutaneous tumors relative to controls were observed, and it is well-tolerated when compared to Doxorubicin and Sorafenib. Transcriptomics analysis using RNA-Seq revealed that genes involved in regulating cell death, cell proliferation, and cellular processes were enriched in a time- and dose-dependent manner. Overall, the cathepsin inhibitor appears to be a promising starting point for further investigation as an antiproliferative agent.
Institutions: University of Alabama in Huntsville, Jackson State University
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Awards: RCN-UBE: HBCU Faculty Collaborative Network for the Integration of Artificial Intelligence and Machine Learning into Teaching General Biology, Distributed Learning for Undergraduate Programs in Data Science at Diverse Universities, RCMI Center for Health Disparities Research, Colorectal Cancer Treatment and Drug Resistance; the Role of IGF2BP1, Mississippi INBRE
OpenAlex ID: W7136336322