山柰酚对前列腺癌骨转移模型小鼠的作用及其机制研究

Effect and mechanism of kaempferol on bone metastasis of prostate cancer in mice

目的通过18F-氟化钠PET CT法研究山柰酚对前列腺癌骨转移模型小鼠的作用及其机制。方法C57BL/6小鼠通过膝关节股骨下端注射RM-1细胞悬浮液建立前列腺癌骨转移小鼠模型。将造模成功小鼠随机分为3组:模型组和低、高2个剂量实验组,另取正常小鼠作为正常组,每组10只。手术后,2个剂量实验组立刻给予山柰酚10,30 mg·kg^-1。以免疫印迹法测定肿瘤组织中的磷酸化细胞外信号调节激酶p-ERK(p-ERK)和磷酸化p-p38(p-p38)蛋白相对表达水平(灰度值),以酶联免疫吸附法测定血清组织中肿瘤坏死因子-α(TNF-α)含量。结果正常组、模型组和低、高2个剂量实验组的p-ERK/ERK比值分别为0.64±0.12,1.25±0.43,0.89±0.36和0.77±0.47;这4组的p-p38/p38比值分别为0.28±0.09,0.75±0.15,0.53±0.24和0.37±0.19;这4组的TNF-α含量分别为(23.43±6.42),(43.93±5.82),(32.48±6.59)和(24.73±7.21)μmo L·L^-1。上述指标:模型组与正常组相比,差异均有统计学意义(P<0.05,P<0.01);低、高2个剂量实验组与模型组相比,差异均有统计学意义(P<0.05,P<0.01)。结论山柰酚可通过调节丝裂原活化蛋白激酶和胞外信号调节激酶以及肿瘤坏死因子-α的表达,发挥抗前列腺癌肿瘤生长的作用。

Objective To explore the effect and mechanism of kaempferol on bone metastasis of prostate cancer in mice by18F-NaF Positron Emission Tomography Computed Tomography(PET CT).Methods A mice model of bone metastasis of prostate cancer was established by injecting RM-1 cell suspension into the lower femur of the knee joint.The 40 C57BL/6 mice successfully modeled were randomly divided into three groups:model group,low and high dose experimental groups,another normal mice as normal group,each group had 10 mice.Immediately after operation,kaempferol solution of 10,30 mg·kg^-1were given to mice of low,high dose experimental groups.The levels of pextracellular regulated protein kinases(ERK),p-mitogen-activated protein kinase(p38)were determined by Western blotting.The content of tumor necrosis factor-α(TNF-α)in serum was determined by enzyme linked immunosorbent assay.Results The p-ERK/ERK ratios in normal group,model group,low and high dose experimental groups were0.64±0.12,1.25±0.43,0.89±0.36,0.77±0.47,respectively;the p-p38/p38 ratios in the four groups were 0.28±0.09,0.75±0.15,0.53±0.24,0.37±0.19,respectively;and the TNF-αcontent in the four groups were(23.43±6.42),(43.93±5.82),(32.48±6.59),(24.73±7.21)μmoL·L^-1,respectively.There were significant differences of the factors between model group and normal group(P<0.05,P<0.01),and there were significant differences of the factors between low,high dose experimental group and model group(P<0.05,P<0.01).Conclusion Kaempferol can inhibit the growth of prostate cancer by regulating the expression of mitogen-activated protein kinase,extracellular signal-regulated kinase and tumor necrosis factor-α.