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

为了检查肿瘤微环境（例如，星形胶质细胞和缺氧）影响胶质母细胞瘤和转移性脑肿瘤对抗癌药物的敏感性，我们测试了在常氧和缺氧条件下与大鼠星形胶质细胞共培养的各种抗癌药物对大鼠和人胶质瘤细胞以及人乳腺癌细胞的细胞毒性活性。结果表明，在星形胶质细胞存在下，替莫唑胺（TMZ）对胶质瘤细胞和转移性脑肿瘤细胞的有效性降低，这不依赖于细胞相互作用或可溶性因子如炎性细胞因子，而主要取决于星形胶质细胞降低TMZ疗效的能力。

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.