The investigating the molecular mechanisms of cognitive impairment due to cancer chemotherapy and its prevention

为探讨化疗所致认知功能障碍的分子机制，我们研究了紫杉醇(PX)、氟尿嘧啶(5-FU)和环磷酰胺(CPA)对培养的神经细胞(SY5Y和SK-N-SH)的神经毒性作用，并进一步探讨了其与内质网应激(ER应激)的关系。在PX和5-FU处理的细胞中可观察到显著的NT，且呈剂量依赖关系，而CPA处理的细胞则无明显变化。另外，PX或5-FU均能诱导p-eIF2α和GRP78/94在细胞中的表达。用Bip诱导剂X(Bix)预先处理细胞可减少PX诱导的NT，但不能减少5-FU诱导的NT。提示Px诱导的NT可能与内质网应激有关，Bix可阻止Px诱导的NT包括化学损伤。

To investigate the molecular mechanisms of chemotherapy induced cognitive impairment, we studied the neuronal toxicity(NT) of paclitaxel(Px), fluorouracil(5-FU), and cyclophosphamide(CPA) on neuronal culture cells(SY5Y and SK-N-SH) and further investigated its relationship to endoplasmic reticulum stress(ER stress). Significant NT was observed in cells treated with Px and 5-FU in dose dependent manner, but not with CPA. In addition, the induction of both p-eIF2αand GRP78/ 94 were observed in cells by Px or 5-FU treatment. Pre-treatment of cells with Bip inducer X(BIX) reduced Px-induced NT but not 5-FU induced NT. These data suggest that Px induced NT probably relates to ER stress and BIX could prevent the Px induced NT as including chemobrain.