3D-bioprinted liver cancer models derived from primary hepatocytes for simulating cancer initiation and drug screening.

BACKGROUND

HCC remains one of the most lethal cancers globally, and accurately replicating the early events of tumor evolution remains a critical challenge.

METHODS

In this study, we developed early-stage liver cancer cell lines by introducing distinct combinations of oncogenes into primary mouse hepatocytes. Using 3D bioprinting technology, combined with bioinks composed of gelatin and alginate, we constructed a more precise representation of liver cancer tissue to better simulate key tumor characteristics.

RESULTS

Our·findings revealed that different oncogene combinations produced unique drug response profiles, with Ras-driven cells exhibiting heightened sensitivity to ferroptosis. Furthermore, 3D bioprinting tumor tissues derived from transformed hepatocytes effectively captured early HCC characteristics. These models preserved key features of early-stage liver cancer and provided a reliable platform for drug screening. Importantly, the 3D models demonstrated higher resistance to chemotherapy and targeted therapies compared with 2D cultures.

CONCLUSIONS

In summary, we established both 2D and 3D models that replicate early HCC progression, offering valuable tools for drug screening and advancing our understanding of early carcinogenic mechanisms.