死亡相关蛋白3参与重组人肿瘤坏死因子-α抑制裸鼠胃癌移植瘤的生长

Recombinant human tumor necrosis factor-αinhibits implanted gastric cancer of node mice via enhancing expression of death associated protein 3

目的观察重组人肿瘤坏死因子-α(rhTNF-α)对荷人胃癌细胞株BGC-823和HGC-27裸鼠移植瘤的生长抑制作用,并检测作用前、后移植瘤中死亡相关蛋白3(DAP3)的表达情况,探讨DAP3在rhTNF-α抑制裸鼠胃癌移植瘤生长中的作用。方法建立荷人胃癌细胞株BGC-823和HGC-27裸鼠移植瘤模型;观察腹腔注射不同剂量的rhTNF-α(0、1、5、10 mg／kg)对裸鼠移植瘤的生长抑制作用,分别采用Western印迹法和逆转录聚合酶链反应(RT-PCR)检测各组裸鼠移植瘤中DAP3蛋白和DAP3 mRNA表达情况。结果①腹腔注射5和10 mg／kg的rhTNF-α,裸鼠荷BGC-823和HGC-27移植瘤的瘤重显著低于对照组(P值均<0．05),而1 mg／kg rhTNF-α组与对照组瘤重的差异无显著性(P>0．05)。②腹腔注射5和10 mg／kg的rhTNF-α4周后,荷人胃癌细胞株BGC-823和HGC-27移植瘤中DAP3蛋白表达显著高于1 mg／kg组和对照组;5和10 mg／kg rhTNF-α可使移植瘤中DAP3 mRNA的表达显著升高。结论DAP3参与rhTNF-α抑制荷人胃癌细胞株BGC-823和HGC- 27裸鼠移植瘤的生长作用,推测DAP3为一新的肿瘤治疗位点。

Objective To observe the therapeutic effects of recombinant human tumor necrosis factor-α（rhTNF-α） on human gastric cancer（BGC-823 and HGC-27） implanted nude mice and to evaluate the role of Death associated protein 3（DAP3） involved. Methods Nude mice model implanted subcutaneously with BGC-823 and HGC-27 was established. Different doses of rhTNF-α（0, 1, 5 and 10 mg/kg） were administrated intraperitoneally and the rates of tumor inhibition measured. The expressions of DAP3 protein and DAP3 rnRNA were determined by Western blot and RT-PCR methods respectively. Results The tumor weights of the 5 mg/kg group and 10 mg/kg group with rhTNF-α were （2.42 ± 0. 31）g and （2.59 ±0.41）g respectively for BGC-823. Both weights of BGC-823 and HGC-27 implanted tumors were significantly smaller than those of the control group, while there was no difference between 1 mg/kg group and the control group. For HGC-27 similar changes occured. DAP3 could not be detected in the control group whereas it could be detected in 5 mg/kg group and 10 mg/kg group by Western blot method. Meanwhile, the expression of DAP3 mRNA increased after being treated with rhTNF-α either at 5 mg/kg or 10 mg/kg dose via RT-PCR method. Conclusions rhTNF-α inhibits implanted gastric cancer of nude mice via enhancing the expression of DAP3, which may be a potential target for gastric cancer treatment. （Shanghai Med J, 2006, 29：744-747）