AUTHOR=Sigdel Indira , Ofori-Kwafo Awurama , Heizelman Robert J. , Nestor-Kalinoski Andrea , Prabhakarpandian Balabhaskar , Tiwari Amit K. , Tang Yuan 

TITLE=Biomimetic on-chip assay reveals the anti-metastatic potential of a novel thienopyrimidine compound in triple-negative breast cancer cell lines

JOURNAL=Frontiers in Bioengineering and Biotechnology

VOLUME=11

YEAR=2023

URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2023.1227119

DOI=10.3389/fbioe.2023.1227119

ISSN=2296-4185

ABSTRACT=<p><bold>Introduction:</bold> This study presents a microfluidic tumor microenvironment (TME) model for evaluating the anti-metastatic efficacy of a novel thienopyrimidines analog with anti-cancer properties utilizing an existing commercial platform. The microfluidic device consists of a tissue compartment flanked by vascular channels, allowing for the co-culture of multiple cell types and providing a wide range of culturing conditions in one device.</p><p><bold>Methods:</bold> Human metastatic, drug-resistant triple-negative breast cancer (TNBC) cells (SUM159PTX) and primary human umbilical vein endothelial cells (HUVEC) were used to model the TME. A dynamic perfusion scheme was employed to facilitate EC physiological function and lumen formation.</p><p><bold>Results:</bold> The measured permeability of the EC barrier was comparable to observed microvessels permeability <italic>in vivo</italic>. The TNBC cells formed a 3D tumor, and co-culture with HUVEC negatively impacted EC barrier integrity. The microfluidic TME was then used to model the intravenous route of drug delivery. Paclitaxel (PTX) and a novel non-apoptotic agent TPH104c were introduced via the vascular channels and successfully reached the TNBC tumor, resulting in both time and concentration-dependent tumor growth inhibition. PTX treatment significantly reduced EC barrier integrity, highlighting the adverse effects of PTX on vascular ECs. TPH104c preserved EC barrier integrity and prevented TNBC intravasation.</p><p><bold>Discussion:</bold> In conclusion, this study demonstrates the potential of microfluidics for studying complex biological processes in a controlled environment and evaluating the efficacy and toxicity of chemotherapeutic agents in more physiologically relevant conditions. This model can be a valuable tool for screening potential anticancer drugs and developing personalized cancer treatment strategies.</p>