Interdisciplinary Program in Neuroscience, George Mason University, Fairfax, VA, United States of America.
School of Systems Biology, George Mason University, Fairfax, VA, United States of America.
PLoS One. 2024 Sep 27;19(9):e0306498. doi: 10.1371/journal.pone.0306498. eCollection 2024.
Paclitaxel is a chemotherapy drug widely used for the treatment of various cancers based on its ability to potently stabilize cellular microtubules and block division in cancer cells. Paclitaxel-based treatment, however, accumulates in peripheral system sensory neurons and leads to a high incidence rate (over 50%) of chemotherapy induced peripheral neuropathy in patients. Using an established preclinical model of paclitaxel-induced peripheral neuropathy (PIPN), we examined proteomic changes in dorsal root ganglia (DRG) of adult male mice that were treated with paclitaxel (8 mg/kg, at 4 injections every other day) relative to vehicle-treated mice. High throughput proteomics based on liquid chromatography electrospray ionization mass spectrometry identified 165 significantly altered proteins in lumbar DRG. Gene ontology enrichment and bioinformatic analysis revealed an effect of paclitaxel on pathways for mitochondrial regulation, axonal function, and inflammatory purinergic signaling as well as microtubule activity. These findings provide insight into molecular mechanisms that can contribute to PIPN in patients.
紫杉醇是一种广泛用于治疗各种癌症的化疗药物，其通过强力稳定细胞微管并阻止癌细胞分裂。然而，基于紫杉醇的治疗方案会在周围系统感觉神经元中积累，导致患者中化疗诱导性周围神经病（chemotherapy induced peripheral neuropathy，CIPN）的发生率很高（超过 50%）。我们使用已建立的紫杉醇诱导性周围神经病（paclitaxel-induced peripheral neuropathy，PIPN）的临床前模型，研究了紫杉醇（8mg/kg，每两天 4 次注射）处理的成年雄性小鼠背根神经节（dorsal root ganglia，DRG）中的蛋白质组变化，并与接受载体处理的小鼠进行了比较。基于液相色谱电喷雾电离质谱的高通量蛋白质组学鉴定出腰椎 DRG 中 165 种明显改变的蛋白质。基因本体论富集和生物信息学分析表明，紫杉醇对线粒体调节、轴突功能和炎症嘌呤能信号转导以及微管活性的途径有影响。这些发现为患者 PIPN 的分子机制提供了深入了解。
