Screening of Chemotherapeutic Drugs Against Colorectal Cancer Based on Different Oxygen Environments in Vitro

Abstract

With the deepening of tumor research, the concept of the tumor microenvironment has gradually come into people’s view. A significant characteristic of the microenvironment is hypoxic. A large number of vitro experiments have confirmed that hypoxic environments can induce angiogenesis, anti-apoptosis, changes in drug sensitivity, and tumor metastasis. Now, chemosensitivity tests are all carried out under normoxic conditions. Therefore, some scholars have pointed out that if it is possible to simulate the hypoxic state of the tumor microenvironment during the chemosensitivity tests in vitro, it may be able to match better the effect of chemotherapeutic drugs on killing tumor cells in vivo. This study clarified the differences in the chemosensitivity for colorectal cancer cells in normoxic and hypoxic environments. The result of CCK-8 detections has shown that the toxicity of drugs to cells is much higher under normoxic conditions. To further figure out the different mechanisms of the chemotherapy drugs under normoxic and hypoxic conditions, we conducted cellular uptake analysis and western blot, which demonstrated that the uptake of Doxorubicin in normoxic cells was significantly higher than that in hypoxic cells. While the result of the western blot has shown that the expression of VDAC (Voltage-dependent anion channel) and cleaved caspase-3 is higher under normoxic conditions. This study provides a specific basis for future research on the chemosensitivity of chemotherapy drugs in hypoxic environments.