Lidocaine induces protective autophagy in rat C6 glioma cell line

利多卡因诱导大鼠 C6 胶质瘤细胞系的保护性自噬

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作者:Magdalena Izdebska, Marta Hałas-Wiśniewska, Wioletta Zielińska, Anna Klimaszewska-Wiśniewska, Dariusz Grzanka, Maciej Gagat

Abstract

Malignant glioma is the most common type of brain cancer with poor prognosis. Surgical resection, chemotherapy and radiotherapy are the main therapeutic options; however, in addition to their insufficient efficacy, they are associated with the pain experienced by patients. To relieve pain, local anesthetics, such as lidocaine can be used. In the present study, the effects of lidocaine on the C6 rat glioma cell line were investigated. An MTT assay and Annexin V/propidium iodide analysis indicated the increase in the percentage of apoptotic and necrotic cells in response to lidocaine. Furthermore, light microscopy analysis on the ultrastructural level presented the occurrence of vacuole‑like structures associated with autophagy, which was supported by the analysis of autophagy markers (microtubule‑associated protein 1A/1B‑light chain 3, acridine orange and Beclin‑1). Additionally, reorganization of the cytoskeleton was observed following treatment with lidocaine, which serves an important role in the course of autophagy. To determine the nature of autophagy, an inhibitor, bafilomycin A1 was applied. This compound suppressed the fusion of autophagosomes with lysosomes and increased the percentage of apoptotic cells. These results demonstrated that lidocaine may induce cytoprotective autophagy and that manipulation of this process could be an alternative therapeutic strategy in the treatment of cancer.

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