枸橼酸芬太尼对裸鼠人胃癌皮下瘤生长的影响

Effects of fentanyl on growth of subcutaneous tumor of human gastric cancer in nude mice

目的探讨枸橼酸芬太尼对裸鼠人胃癌皮下瘤生长的影响。方法 30只BALB/c雄性裸鼠建立人胃癌MGC-803细胞皮下瘤模型,随机分为空白对照组(C组)、生理盐水组(N组)、0.05mg/kg芬太尼组(F1组)、0.1mg/kg芬太尼组(F2组)、0.2mg/kg芬太尼组(F3组)、0.4mg/kg芬太尼组(F4组),每组5只。成瘤后,C组不做任何处理,N、F1、F2、F3和F4组每天分别腹腔注射1.5ml/kg生理盐水、0.05mg/kg芬太尼、0.1mg/kg芬太尼、0.2mg/kg芬太尼、0.4mg/kg芬太尼,连续14d。每2天测量一次肿瘤的长径和短径,计算肿瘤相对体积(RTV);用药结束后拉颈处死裸鼠,半定量逆转录-聚合酶链反应(RT-PCR)和蛋白印迹法(Western blot)检测肿瘤组织中Bcl-2、Bax mRNA和蛋白的表达。结果 F1、F2、F3和F4组最后一次测得的裸鼠皮下瘤RTV分别为(2.03±0.52)、(2.09±0.46)、(2.25±0.26)、(2.56±0.54),明显小于C组的RTV(3.36±0.68)和N组的(3.19±0.60)(P<0.05),而N组与C组差异无统计学意义。与C组和N组比较,F1、F2、F3和F4组裸鼠人胃癌皮下瘤组织Bcl-2mRNA和蛋白表达明显降低,Bax mRNA和蛋白表达明显增加(P<0.05);N组和C组差异无统计学意义。结论枸橼酸芬太尼可抑制裸鼠人胃癌皮下瘤的生长,其机制可能与下调Bcl-2的表达、上调Bax的表达有关。

Objective To investigate the effects of fentanyl on growth of subcutaneous tumor of human gastric cancer in nude mice.Methods BALB/c nude mice were inoculated subcutaneously with MGC-803 cells to establish the subcutaneous tumor model of human gastric carcinoma.After the model was successfully established,30 mice were randomly divided into 6groups（n=5in each group）：control group（group C）,normal saline group（group N）,0.05 mg/kg fentanyl group（group F1）,0.1mg/kg fentanyl group（group F2）,0.2mg/kg fentanyl group（group F3）,and 0.4mg/kg fentanyl group（group F4）.After the diameter of tumor reached to 1.0cm×1.0cm in length and width,mice in group C received no treatment while mice in group N,group F1,group F2,group F3 and group F4 were injected with 1.5ml/kg saline,0.05mg/kg fentanyl,0.1mg/kg fentanyl,0.2mg/kg fentanyl or 0.4mg/kg fentanyl every day,respectively.The caliper was used to measure the tumor size every other day.The relative volume（RTV）was calculated.After 14 days,the nude mice were killed Bcl-2and Bax mRNA and protein expression were detected by semi-quantitative reverse transcription polymerase chain reaction（RT-PCR）and Western blot analysis.Results After 14 days of drugs intervention,tumor relative volume（RTV）in group F1,group F2,group F3 or group F4were（2.03±0.52）,（2.09±0.46）,（2.25±0.26）or（2.56±0.54）respectively which was less than that in group C（3.36±0.68）and group N（3.19±0.60）（P〈0.05）.Compared with that in group C,Bcl-2mRNA and protein in fentanyl groups were downegulated while Bax mRNA and protein expression were upregulated（P〈0.05）.There were no significant differences in RTV,Bcl-2and Bax expression between group C and group N.Conclusion Fentanyl could inhibit the growth of subcutaneous tumor of human gastric cancer in nude mice,which might be related with Bcl-2downregulation and Bax upregulation.