益肾通癃汤对前列腺癌裸鼠模型Nrf-2、SOD1的影响

Effects of Yishen Tonglong Decoction on Nrf-2 and SOD1 in Nude Mice Model of PCa

目的:探讨益肾通癃汤对前列腺癌(prostate cancer,PCa)裸鼠模型核因子红细胞2相关因子2(Nrf-2)和超氧化物歧化酶1(SOD1)的影响。方法:SPF级雄性裸鼠接种PC-3细胞悬液,造模成功后随机分为模型组,益肾通癃汤低、中、高剂量组。模型组灌胃生理盐水[1 mL/(100 g·d)],益肾通癃汤各剂量组分别采用0.72、1.44、2.88 g/mL的益肾通癃汤灌胃[1 mL/(100 g·d)],灌胃21 d后处死裸鼠,称取瘤体质量计算抑瘤率,镜下观察病理改变,ELISA检测Nrf-2、SOD1表达量,WB(Western blot)、RTPCR检测Nrf-2、SOD1蛋白及mRNA表达。结果:与模型组比较,益肾通癃汤各剂量组抑瘤率升高(P <0.05,P <0.01),镜下观察细胞核裂解明显,可下调Nrf-2、SOD1蛋白及mRNA的表达(P <0.05,P <0.01);上述结果均呈浓度依赖性。结论:益肾通癃汤可能是通过抑制Nrf-2、SOD1的表达,诱导癌细胞氧化应激反应,达到对PCa的治疗作用。

Objective: To investigate the effects of Yishen Tonglong Decoction on nuclear factor erythrocyte 2 related factor 2(Nrf-2) and superoxide dismutase 1(SOD1) in nude mice model of prostate cancer(PCa). Methods: SPF grade male nude mice were inoculated with PC-3 cell suspension. After successful modeling, they were randomly divided into the model group, the Yishen Tonglong Decoction groups of low-dose, medium-dose and high-dose. The model group was gavaged with normal saline(1 mL/100g·d).The experimental groups were gavaged with Yishen Tonglong Decoction(1 mL/100g·d) at the dose of 0. 72 g/mL, 1. 44 g/mL and 2. 88 g/mL, respectively. After gavage for 21 days, the nude mice were killed, the tumor mass was weighed to calculate the tumor inhibition rate, the pathological changes were observed under microscope, the contents of Nrf-2 and SOD1 were detected by ELISA, and the protein and mRNA expressions of Nrf-2 and SOD1 were detected by Western blot and RT-PCR. Results: Compared with those in the model group, the tumor inhibition rate increased(P<0.05, P<0.01), the nuclear lysis was obvious under microscope, and the protein and mRNA expressions of Nrf-2 and SOD1 were down-regulated in the Yishen Tonglong Decoction groups(P<0.05, P<0.01);which showed concentration-dependent effect. Conclusion: Yishen Tonglong Decoction may induce oxidative stress response of cancer cells by inhibiting the expressions of Nrf-2 and SOD1 in treatment of PCa.