Drug screenings in microfluidics with different oxygen tension

Abstract

Malignant tumors have been identified as a major cause of many deaths, and the mortality rate is increasing every year. Investments and spending on cancer treatments are increasing over the years, and the scale and importance of research on cancer chemotherapy are increasing. In particular, breast cancer is more likely to lead to death because it has a higher metastatic potential than other types of cancer. Cancer cells in the body mainly exist in a cluster, so they have lower oxygen tension than the surrounding environment. Therefore, this study aims to compare the efficacy of anticancer drugs as the oxygen tension changes based on the microfluidic device which is easy to form an oxygen tension gradient. A microfluidic device with channels through which gas flows are designed in addition to channels for culturing cells. Simulations and experiments using oxygen sensitive fluorescence reagents were performed to confirm that the desired oxygen tension gradient was formed. Breast cancer cells (MDA-MB-231s) and human umbilical vein endothelial cells were co-cultured in the microfluidic device to mimic the microenvironment surrounding the cancer cells in the body. In order to confirm the cell response to changes in oxygen tension in the device, the difference of the expression level of hypoxic environment specific marker (HIF-1$\alpha$) and the motility of the cancer cells according to the oxygen tension was observed. Finally, comparing the viability of the cancer cells by the two anti-cancer drugs in different oxygen tension confirmed that the oxygen tension could affect the anti-cancer effect. In conclusion, we confirmed the effect of anti-cancer drugs in oxygen tension gradient generated environment by simulating the microenvironment similar to the body by controlling the oxygen tension in the device and suggested the need to control the dosage of anti-cancer drugs which may be harmful to human normal tissues.