摘要
目的探讨不同剂量卡非佐米对多发性骨髓瘤大鼠基质细胞衍生因子-1(SDF-1)和趋化因子受体(CXCR4)表达水平的影响及相关作用机制。方法随机选取50只健康SD大鼠中10只为空白组,其余40只大鼠进行多发性骨髓瘤模型建造,空白组大鼠不做处理。建模成功后,随机选取10只大鼠作为模型组,其余30只大鼠为给药组,对给药组大鼠采用不同剂量的卡非佐米进行干预,并根据使用剂量将给药组大鼠分为低剂量组、中剂量组、高剂量组,每组各10只,并对低、中、高剂量组大鼠分别采用1.5、2.5、3.5mg/mL的卡非佐米进行干预,21d后处死大鼠,并对其皮下瘤组织进行切片染色观察,测量5组大鼠荷瘤重量平均值、腹水量平均值和肿瘤体积,采用免疫投射比浊法对5组大鼠SDF-1、CXCR4水平进行检测,酶联免疫吸附法检测核因子-κB(NF-κB)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和类胰岛素一号增长因子(IGF-1)表达水平,并阐述卡非佐米的治疗机制。结果中剂量组大鼠的荷瘤重量平均值、腹水量平均值和肿瘤体积明显低于低剂量组和高剂量组,且SDF-1、CXCR4表达水平亦显著低于低剂量组和高剂量组(均P<0.05);中剂量组大鼠NF-κB、IL-6、TNF-α和IGF-1表达水平较低、高剂量组显著降低(均P<0.05)。结论卡非佐米能降低SDF-1、CXCR4水平的表达,抑制炎症通路活性来控制瘤细胞增殖,且中剂量卡非佐米的抑制效果更明显,可为临床用药提供一定的理论依据。
ObjectiveTo study the effects of different doses of carfezomib on the expression of stromal cell-derived factor-1 (SDF-1) and chemokine receptor (CXCR4) in multiple myeloma rats and the related mechanisms. Methods50 healthy SD rats were selected and randomly divided into blank group, model group, low dose group, medium dose group and high dose group. Multiple myeloma model was built in model group and low, medium and high dose group. After the success of the modeling of low, medium and high dose group of rats with different doses of card of meters to intervene, 21 d after the death of the subcutaneous tumor tissue biopsy staining observation, measuring 5 groups rats tumor-burdened average weight, abdomen water mean and tumor size, the project immune turbidimetric method is adopted to 5 groups of rats SDF-1 and CXCR4 level testing, using enzyme-linked immunosorbent method to detect Nuclear factor kappa B predominate-(Nuclear factor-κB, NF-KB), Interleukin-6 (Interleukin 6,IL-6), Tumor necrosis factors-α(TNF-α) and insulin-like growth factor-1 (IGF-1) to elucidate the therapeutic mechanism of carfi zolmi. ResultsThe mean tumor-bearing weight, abdominal water volume and tumor volume of rats in the medium dose group were significantly lower than those in the low dose group and the high dose group. The expression levels of sdf-1 and CXCR4 in the medium dose group were significantly lower than those in the low dose and high dose groups. The expression levels of NF-κB, il-6, TNF-α, and IGF-1 in rats in the medium dose group were significantly lower than those in the high dose group, and the differences were statistically significant. ConclusionCarfizo can reduce the expression level of SDF-1 and CXCR4, inhibit the inflammatory pathway activity to control tumor cell proliferation, and the inhibitory effect of carfizo at medium dose is more obvious, providing a certain theoretical basis for clinical medication.
作者
张冲
蔡执中
汤健
何春辉
陶飞飞
ZHANG Chong;CAI Zhizhong;TANG Jian;HE Chunhui;TAO Feifei(Department of Orthopedics ,Haimen People’s Hospital, Haimen 226100, Jiangsu, China;Department of Orthopedics, Armed Police Hospital of Jiaxing, Jiaxing 314000, Zhejiang, China)
出处
《西部医学》
2019年第8期1196-1200,共5页
Medical Journal of West China
