MAP2K6-FP和紫杉醇对上皮性卵巢癌裸鼠移植瘤的抑制作用

目的:研究靶向融合肽MAP2K6-FP（mitogen-activated protein kinase kinase 6-fusion protein)、紫杉醇单独和两者联合对上皮性卵巢癌裸鼠移植瘤的抑制作用。方法:建立卵巢癌HO8910细胞的裸鼠皮下移植瘤模型，分为空白对照组（予生理盐水 5 ml/kg腹腔注射治疗）、MAP2K6-FP组（予0.25 mg/kg MAP2K6-FP腹腔注射治疗）、紫杉醇组（予15 mg/kg 紫杉醇腹腔注射治疗）、联合用药组（予0.25 mg/kg MAP2K6-FP+15 mg/kg 紫杉醇腹腔注射治疗），比较4组裸鼠的移植瘤生长速度、体积、裸鼠体质量；TUNEL法、免疫组织化学法和蛋白印迹法分别检测移植瘤中细胞凋亡情况、血管内皮生长因子（vascular endothelial growth factor，VEGF）、增殖细胞核抗原（proliferating cell nuclear antigen，PCNA）的表达以及Bcl-2、Beclin 1蛋白的表达。结果:联合用药组裸鼠移植瘤体积（90 mm3），小于MAP2K6-FP组（324 mm3）、紫杉醇组（215 mm3）和空白对照组（804 mm3）（P<0.05）。联合用药组肿瘤细胞的凋亡指数（apoptosis index，AI）(28.88±2.03)%，高于MAP2K6-FP组(14.36±0.56)%、紫杉醇组(15.78±0.87)%以及空白对照组(4.78±0.87)%（P<0.05）。联合用药组VEGF蛋白表达水平(0.14±0.06)，低于MAP2K6-FP组(0.32±0.10)、紫杉醇组(0.29±0.08)及空白对照组(0.78±0.14）（P<0.01)；联合用药组PCNA表达水平(18.4%)，低于MAP2K6-FP组(32.3%)、紫杉醇组(29.8%)及空白对照组(81.4%）（P<0.05）。联合用药组Beclin 1/Bcl-2比例较单一用药组高(P<0.05)。结论:MAP2K6-FP联合紫杉醇能够显著抑制卵巢癌裸鼠移植瘤的生长，其机制可能与促进细胞凋亡有关。

Inhibition effect of mitogen-activated protein kinase kinase 6-fusion protein (MAP2K6-FP) and paclitaxel on human ovarian cancer in nude mice xenograft

Objective:To investigate the inhibition effect of a mitogen-activated protein kinase (MAPK) kinase fusion protein and paclitaxel on human ovarian cancer in nude mice xenograft.Methods:The subcutaneous xenograft tumor model of human ovarian cancer HO8910 cells in nude mice was established.Then the tumor-bearing nude mice were randomly assigned to four groups:Blank control group (the saline was administered intraperitoneally)，MAP2K6-FP group(MAP2K6-FP was administered intraperitoneally)，paclitaxel group(paclitaxel was administered intraperitoneally)，combination group(MAP2K6-FP+paclitaxel was administered intraperitoneally).The tumor growth，tumor volume and body weight of nude mice of four groups were observed.The apoptosis and the expressions of vascular endothelial growth factor (VEGF)，proliferating cell nuclear antigen(PCNA) and Beclin 1/Bcl-2 of xenograft tumors were examined by TUNEL method，immunohistochemistry and western blotting，respectively.Results:Compared with MAP2K6-FP group，paclitaxel group and control group，the growth rate of xenograft in combination group was decreased significantly （P<0.05).The volume of xenograft tumor and the body weight of nude mice in combination group were decreased significantly as compared with those in the MAP2K6-FP group，paclitaxel group and control group（both P<0.05).The apoptosis index (AI） value in combination group was higher than those in the MAP2K6-FP group，paclitaxel group and control group （P<0.05).The positive rate of VEGF，PCNA expression in the combination group was lower than those in the MAP2K6-FP group，paclitaxel group and control group，and the expression level of Beclin 1/Bcl-2 was opposite(all P<0.05).Conclusion:MAP2K6-FP and paclitaxel can significantly inhibit the growth of subcutaneous xenograft tumor of ovarian cancer in nude mice.This effect may be related to promoting apoptosis.