Exploring cancer-associated fibroblast-induced resistance to tyrosine kinase inhibitors in hepatoma cells using a liver-on-a-chip model
Madhu Shree Poddar, Yu‐De Chu, Gaurav Pendharkar, Cheng‐Hsien Liu, Chau‐Ting Yeh
Abstract
values of sorafenib and lenvatinib in 2D co-culture, a transwell setup revealed drug resistance development in co-cultured cells. Within the 3D microfluidic chip, live/dead assays highlighted elevated viability under drug exposure, emphasizing fibroblast-driven drug resistance. The study identifies AHSG and CLEC3B as potential mediators of drug resistance in co-culture, significantly upregulated in the co-cultured medium. Functional tests confirmed their roles, as introducing recombinant AHSG and CLEC3B enhanced liver cancer cell resistance to sorafenib and lenvatinib in both 2D and 3D scenarios. In conclusion, by replicating the complex TME using microfluidic technology, this study sheds light on the roles of AHSG and CLEC3B as well as possible approaches for improving the effectiveness of liver cancer treatment.