Anti-cancer drug evaluation in liver cancer on a chip

Title: Anti-cancer drug evaluation in liver cancer on a chip. Aim: In recent years, on-chip cancer models based on microfluidics have become effective tools to investigate the tumor microenvironment, its role in metastasis and rapidly evaluate the efficacy of cancer drugs. In this thesis, a liver cancer model was formed on a chip platform, and the effect of known anticancer agents as curcumin and cyclophosphamide with their combination was investigated. Methods: The cytotoxic effect of curcumin, cyclophosphamide and their combination on cells was investigated by MTT cytotoxicity assay. Then, the apoptotic and toxic effect was investigated by live/dead-staining, immunofluorescence-staining (caspase-3, caspase-8, AFP, CK18) methods in static and dynamic culture. Results: According to MTT analysis, after 24 hours IC50 values of 80 µM for curcumin, 3 mM for Cyclophosphamide and 60 µM/1,5 mM for combination were used for further characterizations. Accordingly, it was observed that the expression of AFP, CK18, active-caspase 3, caspase 8 biomarkers changed with the IF method. According to the live/dead staining results, it was observed that cell viability decreased with the active dose, and although there was a significant decrease in the number of cells with the combination of curcumin and CYP, cell viability increased in the microfluidic culture environment compared to the static culture environment. Conclusion: Curcumin, CYP, and the combination of curcumin exhibit anti-cancer activity in a chip platform model that mimics the microphysiology of liver cancer. Consequently, the data obtained suggest that the liver cancer chip platform, developed as a next-generation model closer to in vivo models, could be a suitable model for testing anti-cancer drug activities in cancer research. Keywords: Liver-cancer-on-a-chip, Cyclophosphamide, curcumin, apoptosis, liver cancer.