Analysis of the effects of tumor microenvironment on the susceptibility of malignant tumors to anticancer drugs-its therapeutic application

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To examine whether tumor microenvironment (e.g., astrocytes and hypoxia) influence the susceptibility of glioblastoma and metastatic brain tumors to anticancer drugs, we tested cytotoxic activity of various anticancer agents against rat and human glioma cells and human mammary carcinoma cells in cocultures with rat astrocytesunder normoxic and hypoxic conditions. The results showed that temozolomide (TMZ) becomes less effective against glioma cells and metastatic brain tumor cells in the presence of astrocytes, which depends not on cellular interactions or soluble factors such as inflammatory cytokines but primarily on the ability of astrocytes to reduce the efficacy of TMZ.