Effect of association of temozolomide with other chemotherapic agents on cell growth inhibition in glioma cell lines

Despite progresses in surgery and treatments of malignant gliomas, prognosis of these tumors remains poor, with a median life expectancy of 12 months in glioblastomas. Chemotherapy (mostly with nitrosoureas) has been demonstrated to prolong overall survival, but the entity of this improvement is slight and disease recurrence/progression is the rule, stressing the need for multimodality treatment. In this work we investigated the effect of association of temozolomide (TMZ), an orally bioavailable alkylating agent, with three chemotherapeutic drugs, liposomal doxorubicin (DOXO), cis-platinum (CDDP), and topotecan (TP), on cell growth of A172, U373, U138, U87, and SW1783 (all human glioma cell lines). Results indicate a synergistic effect (CI < 1) of TMZ in association with liposomal DOXO and CDDP on cell growth inhibition in most of the studied cell lines (A172, U373, U138, U87). Synergistic effect also has been obtained after treatment of A172 and U373 with TMZ and TP in association. In conclusion, our results confirm the potential effect of association of chemotherapic drugs with different mechanisms of action in the treatment of gliomas.