Combination of temozolomide and Taxol exerts a synergistic inhibitory effect on Taxol-resistant glioma cells via inhibition of glucose metabolism

摘要

Malignant gliomas, which comprise the most common type of primary malignant brain tumor, are associated with a poor prognosis and quality of life. Paclitaxel (Taxol) and temozolomide (TMZ) are Food and Drug Administration-approved anticancer agents, which are known to have therapeutic applications in various malignancies. However, similar to other chemotherapeutic agents, the development of resistance to TMZ and Taxol is common. The aim of the present study was to investigate the regulation of glucose metabolism by TMZ and Taxol in glioma cells. The results demonstrated that glioma cells exhibit decreased glucose uptake and lactate production in response to treatment with TMZ; however, glucose metabolism was increased in response to Taxol treatment. Following analysis of TMZ- and Taxol-resistant cell lines, it was reported that glucose metabolism was decreased in the TMZ-resistant cells, but was increased in the Taxol-resistant cells. Notably, a combination of TMZ and Taxol exerted synergistic inhibitory effects on Taxol-resistant glioma cells. However, the synergistic phenotype was not observed following treatment with a combination of 5-fluorouracil and Taxol. Furthermore, restoration of glucose metabolism by overexpression of glucose transporter 1 in Taxol-resistant cells resulted in regained resistance to Taxol. Therefore, the present study proposes a novel mechanism accounting for the synergistic effects of Taxol and TMZ co-treatment, which may contribute to the development of therapeutic strategies for overcoming chemoresistance in patients with cancer.