奥沙利铂对二甲肼诱导的结肠癌大鼠CD44V6、VEGF、survivin、Caspase-3和Caspase-7的影响

doi:10.3971/j.issn.1000-8578.2015.06.006

奥沙利铂对二甲肼诱导的结肠癌大鼠CD44V6、VEGF、survivin、Caspase-3和Caspase-7的影响

Effect of Oxaliplatin on CD44V6, VEGF, survivin, Caspase-3 and Caspase-7 in Dimethylhydrazine-induced Colon Cancer Rats

摘要

摘要: 目的研究奥沙利铂对结肠癌大鼠治疗的作用机制。方法将42只SD大鼠均颈背部皮下注射二甲肼，每周注射 1次，连续注射5周。随机抽取2只大鼠切取直肠进行HE染色，病理学观察，确定结肠癌大鼠模型建立。将40只结肠癌大鼠随机分为模型组、奥沙利铂高、中、低剂量组，每组10只。另设正常组SD大鼠10只。奥沙利铂高剂量组（27.2 mg/kg）、中剂量组（13.6 mg/kg）、低剂量组（6.8 mg/kg），给予1 ml 5%的葡萄糖注射液溶解，尾静脉注射给药，每3周给药一次，连续给药12周。正常组与模型组给予1 ml 5%的葡萄糖注射液代替。末次给药48 h后，通过颈脱位法处死大鼠。显微镜观察结肠组织中异变腺窝病灶(ACF)的个数。通过酶联免疫吸附（ELISA）法检测结肠癌大鼠血清中CD44V6和VEGF的含量变化。免疫蛋白印记（Western blot）法检测结肠癌组织中survivin、Caspase-3和Caspase-7的蛋白水平。结果与模型组比较，奥沙利铂给药组结肠组织中ACF的数量明显减少。与正常对照组比较，模型组血清中CD44V6和VEGF的含量显著增加（P＜0.05）。与模型组相比，奥沙利铂高剂量组、中剂量组血清中CD44V6和VEGF的含量下降。其中奥沙利铂高剂量的效果最好，差异有统计学意义（P＜0.05）。与正常组相比，模型组、奥沙利铂给药组结肠癌组织中的survivin、Caspase-3和Caspase-7的蛋白水平均上升。与模型组相比，奥沙利铂给药组结肠癌组织中的survivin的蛋白水平降低；Caspase-3和Caspase-7的蛋白水平升高，差异有统计学意义（P＜0.05）。结论奥沙利铂通过调控CD44V6、VEGF、survivin、Caspase-3和Caspase-7的水平，减少肿瘤血管的生成与转移、调节结肠癌组织中的细胞凋亡，从而达到治疗的目的。

Abstract: Objective To investigate the effect and mechanism of oxaliplatin on colon cancer in rats. Methods Forty-two SD rats were subcutaneous injected with dimethylhydrazine, once a week, continuously for 5w. The establishment of colon cancer model was determined by pathological observation through rectum HE staining of 2 rats randomly. The rest of 40 colon cancer rats were randomly divided into the following four groups containing 10 rats per group: model group, oxaliplatin high-dose, medium-dose and low-dose groups. Normal group contained 10 SD rats. The 1 ml 5% glucose injection solutions of oxaliplatin were injected into the rats tail vein in oxaliplatin groups(27.2, 13.6, 6.8 mg/kg), once every three weeks, continuously for 12 w. Normal group and model group were injected with 1 ml 5% glucose injection. The rats were sacrificed by cervical dislocation 48 hours after the last administration. The number of colon tissue mutation crypt foci (ACF) was observed by microscope. ELISA was used to detect the change of serum CD44v6 and VEGF levels. Caspases-3, Caspases-7 and survivin expression were assessed by Western blot. Results Compared with the model group, the number of ACF in colonic tissues in oxaliplatin treatment groups was significantly reduced. Compared with normal group, the serum CD44V and VEGF levels in model group were significantly increased(P＜0.05). While compared with the model group, the serum contents of CD44V and VEGF in oxaliplatin high-dose and medium-dose groups were decreased, especially oxaliplatin high-dose group showed better effect on that, and the difference was statistically significant(P＜0.05). Compared with normal group, the expression of survivin, Caspase-3 and Caspases-7 proteins in colonic tissues were up-regulated in the rats of model group and oxaliplatin groups. Compared with model group, the protein expression of survivin were reduced by oxaliplatin treatment, meanwhile, the expression of Caspases-3, Caspases-7 protein were enhanced significantly (P<0.05). Conclusion The effect of oxaliplatin on colon cancer is associated with ameliorating the carcinoma angiogenesis and metastasis, inhibiting cell apoptosis in colon tissues through regulating the levels of CD44V6, VEGF, survivin, Caspase-3 and Caspase-7.

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