Guan Ding-Guo, Chen Han-Min, Liao Sheng-Fang, Zhao Tian-Zhi
Department of Neurosurgery, The 180th Hospital of PLA, Quanzhou, Fujian 362000, P.R. China.
Department of Neurosurgery, Affiliated Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shanxi 710038, P.R. China.
Mol Med Rep. 2015 Nov;12(5):7705-11. doi: 10.3892/mmr.2015.4405. Epub 2015 Oct 1.
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.
恶性胶质瘤是最常见的原发性恶性脑肿瘤类型,其预后和生活质量较差。紫杉醇(泰素)和替莫唑胺(TMZ)是美国食品药品监督管理局批准的抗癌药物,已知它们在各种恶性肿瘤中具有治疗应用。然而,与其他化疗药物类似,对TMZ和紫杉醇产生耐药性是常见的。本研究的目的是研究TMZ和紫杉醇对胶质瘤细胞葡萄糖代谢的调节作用。结果表明,胶质瘤细胞在接受TMZ治疗后,葡萄糖摄取和乳酸生成减少;然而,在接受紫杉醇治疗后,葡萄糖代谢增加。在分析对TMZ和紫杉醇耐药的细胞系后,据报道,对TMZ耐药的细胞中葡萄糖代谢减少,但对紫杉醇耐药的细胞中葡萄糖代谢增加。值得注意的是,TMZ和紫杉醇联合使用对耐紫杉醇的胶质瘤细胞具有协同抑制作用。然而,5-氟尿嘧啶和紫杉醇联合治疗后未观察到协同表型。此外,在耐紫杉醇的细胞中过表达葡萄糖转运蛋白1恢复葡萄糖代谢,导致对紫杉醇重新产生耐药性。因此,本研究提出了一种新的机制来解释紫杉醇和TMZ联合治疗的协同作用,这可能有助于制定克服癌症患者化疗耐药性的治疗策略。