Department of Anesthesiology and Pain Medicine, The First Affiliated Hospital of Jiaxing University, Jiaxing, 314001, China.
Department of Central Laboratory, The First Affiliated Hospital of Jiaxing University, Jiaxing, 314001, China.
Neurosci Lett. 2019 Apr 23;699:151-159. doi: 10.1016/j.neulet.2019.01.045. Epub 2019 Jan 29.
Treatment of cancer-induced bone pain (CIBP) is challenging in clinics. Oxycodone is used to treat CIBP. However, the lack of understanding of the mechanism of CIBP limits the application of oxycodone. In this study, proteomic profiling of oxycodone-treated spinal dorsal cord of rats with CIBP was performed. Briefly, a total of 3519 proteins were identified in the Sham group; 3505 proteins in the CIBP group; and 3530 proteins in the CIBP-OXY treatment group. The 2-fold cut-off value was used as the differential protein standard for abundance reduction or increase (p < 0.05). Significant differences were found in the abundance of 16 proteins between Sham and CIBP group; 11 proteins in the CIBP group had increased abundance while 5 proteins had reduced abundance. Furthermore, fifteen proteins with differential abundance were identified between the CIBP group and the OXY group. Compared with the CIBP group, there were six increased abundances and nine reduced abundances in the OXY group. In addition, a reduced expression of ADP-ribosylation factor-like 6 binding factor 1 (Arl6ip-1), an endoplasmic reticulum protein that has an important role in cell conduction and material transport, was found in the CIBP group compared with the Sham group. Its expression increased after the administration of OXY. Proteomics results were further verified by Western-blot. Fluorescent staining revealed that Arl6ip-1 co-localized with spinal dorsal horn neurons, but not with astrocytes or microglia. Based on the observed results, we believe that Arl6ip-1 may be a potential drug target for OXY treatment of CIBP rats.
癌症骨痛（CIBP）的治疗在临床上具有挑战性。羟考酮用于治疗 CIBP。然而，对 CIBP 机制的认识不足限制了羟考酮的应用。在这项研究中，对 CIBP 大鼠脊髓背根中羟考酮处理的蛋白质组进行了分析。简而言之，在 Sham 组中鉴定出 3519 种蛋白质；CIBP 组中有 3505 种蛋白质；CIBP-OXY 治疗组中有 3530 种蛋白质。使用 2 倍的截止值作为丰度降低或增加的差异蛋白标准（p < 0.05）。在 Sham 和 CIBP 组之间的丰度中发现了 16 种蛋白质存在显著差异；在 CIBP 组中，11 种蛋白质的丰度增加，而 5 种蛋白质的丰度减少。此外，在 CIBP 组和 OXY 组之间还鉴定出 15 种具有差异丰度的蛋白质。与 CIBP 组相比，OXY 组中有 6 种蛋白质的丰度增加，9 种蛋白质的丰度减少。此外，与 Sham 组相比，CIBP 组中一种重要的细胞传导和物质运输的内质网蛋白 ADP-核糖基化因子样 6 结合因子 1（Arl6ip-1）的表达减少。在用 OXY 处理后，其表达增加。蛋白质组学结果通过 Western-blot 进一步验证。荧光染色显示，Arl6ip-1 与脊髓背角神经元共定位，而不与星形胶质细胞或小胶质细胞共定位。基于观察到的结果，我们认为 Arl6ip-1 可能是 OXY 治疗 CIBP 大鼠的潜在药物靶点。
