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羟基磷灰石纳米颗粒经静脉注射对兔移植性肝VX2肿瘤生长及p53/c-Myc蛋白表达的影响

Effect of hydroxyapatite nanoparticles on the growth and p53/c-Myc protein expression of implanted hepatic VX2 tumor in rabbits by intravenous injection.

作者信息

Hu Jun, Liu Zhi-Su, Tang Sheng-Li, He Yue-Ming

机构信息

Department of General Surgery, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, China.

出版信息

World J Gastroenterol. 2007 May 28;13(20):2798-802. doi: 10.3748/wjg.v13.i20.2798.

Abstract

AIM

To evaluate the effect of hydroxyapatite nano-particles (Nano HAP) by intravenous injection on the inhibition of implanted hepatic VX(2) tumor growth in rabbits and cell p53/c-Myc protein expression.

METHODS

60 hepatic VX(2) tumor-bearing rabbits was randomly divided into five groups. Nano HAP collosol 20 mg/kg, 40 mg/kg, 5-FU solutions 20 mg/mL, mixed liquor of 5-FU solution 20 mg/mL and Nano HAP collosol 20 mg/kg were infused by vein, normal saline conducted as the control. The general state, weight, liver function and gross tumor volume were detected dynamically. The expression of p53 and c-Myc gene protein in tumor tissue was detected by immunohistochemistry methods.

RESULTS

The growth of implanted hepatic VX(2) tumors was significantly inhibited in all therapy groups, 3 wk after the injection, the tumor control rates in Nano HAP collosol groups were 25.5% and 32.5% respectively, and the gross tumor volumes were obviously less than that of control group. (24.81 +/- 5.17 and 22.73 +/- 4.23 vs 33.32 +/- 5.26, P<0.05). The tumor control rate of 5-FU group was 43.7% (18.74 +/- 4.40 vs 33.32 +/- 5.26, P<0.05), but the general state of the animals after injection aggravated; and the adverse reaction in the drug combination group obviously decreased. Due to the effect of Nano HAP, the positive expression of tumor associated the mutated p53 and c-Myc in tumor tissue was decreased obviously compared with the control group.

CONCLUSION

Nano HAP has evident inhibitory action on rabbit implanted hepatic VX(2) tumor in vivo, which may be the result of decreasing the expression of the mutated p53 and c-myc, and drug combination can obviously decrease the adverse reaction of 5-FU.

摘要

目的

评价静脉注射纳米羟基磷灰石(Nano HAP)对兔移植性肝VX(2)肿瘤生长的抑制作用及对细胞p53/c-Myc蛋白表达的影响。

方法

将60只荷肝VX(2)肿瘤兔随机分为5组。分别静脉输注20mg/kg、40mg/kg的Nano HAP溶胶、20mg/mL的5-氟尿嘧啶(5-FU)溶液、20mg/mL的5-FU溶液与20mg/kg的Nano HAP溶胶混合液,以生理盐水作为对照。动态检测一般状态、体重、肝功能及肿瘤大体体积。采用免疫组织化学方法检测肿瘤组织中p53和c-Myc基因蛋白的表达。

结果

各治疗组移植性肝VX(2)肿瘤生长均受到明显抑制,注射后3周,Nano HAP溶胶组的肿瘤控制率分别为25.5%和32.5%,肿瘤大体体积明显小于对照组(24.81±5.17和22.73±4.23 vs 33.32±5.26,P<0.05)。5-FU组的肿瘤控制率为43.7%(18.74±4.40 vs 33.32±5.26,P<0.05),但注射后动物一般状态加重;药物联合组的不良反应明显减轻。由于Nano HAP的作用,与对照组相比,肿瘤组织中与突变型p53和c-Myc相关的肿瘤阳性表达明显降低。

结论

Nano HAP对兔移植性肝VX(2)肿瘤具有明显的体内抑制作用,可能是降低突变型p53和c-myc表达的结果,药物联合可明显减轻5-FU的不良反应。

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