Department of Histology and Embryology, Faculty of Medicine, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, 85-092 Bydgoszcz, Poland.
Department of Clinical Pathomorphology, Faculty of Medicine, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, 85-092 Bydgoszcz, Poland.
Int J Oncol. 2019 Mar;54(3):1099-1111. doi: 10.3892/ijo.2018.4668. Epub 2018 Dec 14.
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.
恶性胶质瘤是最常见的脑癌类型，预后不良。手术切除、化疗和放疗是主要的治疗选择；然而，除了疗效不足外，它们还与患者的疼痛有关。为了缓解疼痛，可以使用局部麻醉剂，如利多卡因。在本研究中，研究了利多卡因对 C6 大鼠胶质瘤细胞系的影响。MTT 检测和 Annexin V/碘化丙啶分析表明，利多卡因处理后凋亡和坏死细胞的百分比增加。此外，在超微结构水平上的光镜分析显示了与自噬相关的空泡样结构的发生，自噬标志物（微管相关蛋白 1A/1B-轻链 3、吖啶橙和 Beclin-1）的分析支持了这一发现。此外，在用利多卡因处理后观察到细胞骨架的重排，这在自噬过程中起着重要作用。为了确定自噬的性质，应用了一种抑制剂，巴弗洛霉素 A1。该化合物抑制了自噬体与溶酶体的融合，并增加了凋亡细胞的百分比。这些结果表明，利多卡因可能诱导细胞保护性自噬，并且操纵该过程可能是癌症治疗的另一种治疗策略。
