从AR/AR-V7信号通路探讨固本清源方联合雄激素剥夺治疗控制去势抵抗性前列腺癌的作用机制  

Exploration of Mechanism of Guben Qingyuan Prescription Combined with Androgen Deprivation Therapy Against Castration-resistant Prostate Cancer from AR/AR-V7 Signaling Pathway

作　　者：陈浩然 方素萍[1] 张迪 王家政 刘浩[1] CHEN Hao-ran;FANG Su-ping;ZHANG Di;WANG Jia-zheng;LIU Hao(Guang'anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China)

机构地区：[1]中国中医科学院广安门医院,北京100053

出　　处：《中国实验方剂学杂志》2021年第15期16-21,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金面上项目(81873171);全国中医药创新骨干人才项目(国中医药人教函[2019]128号)。

摘　　要：目的:探讨固本清源方联合雄激素剥夺治疗(ADT)控制去势抵抗性前列腺癌作用及其机制。方法:建立去势抵抗性前列腺癌荷瘤小鼠模型,当瘤体体积达到100 mm3时,将50只BALB/c裸鼠随机分为模型组,ADT组,ADT+固本清源方低、中、高剂量组5组,每组10只小鼠,分组后保证各组动物之间,肿瘤体积差异无统计学意义。模型组给予等量生理盐水(10 mL·kg^(-1))灌胃,每日灌胃2次;其余组均给予比卡鲁胺(5 mg·kg^(-1))灌胃,每日1次,第10天腹腔注射醋酸戈舍瑞林(0.36 mg·kg^(-1));固本清源方组在ADT的基础上同时给予固本清源方低、中、高剂量(2.5,25,50 g·kg^(-1))灌胃,每日灌胃2次。连续给药25 d后剥离瘤体组织,记录荷瘤小鼠肿瘤的生长情况、计算肿瘤抑制率;采用实时荧光定量聚合酶链式反应(Real-time PCR)和蛋白免疫印迹法(Western blot)分别检测肿瘤组织中雄激素受体(AR),雄激素受体剪接变异体-7(AR-V7),前列腺癌特异性抗原(PSA)的mRNA及蛋白表达。结果:ADT+固本清源方低、中、高剂量组的抑瘤率分别为27.95%,46.71%,44.46%,与ADT组比较,中、高剂量组抑瘤率明显升高(P<0.05)。进一步研究显示,与ADT组比较ADT+固本清源方中、高剂量组能明显下调AR,AR-V7,PSA的mRNA及蛋白表达水平(P<0.05)。结论:固本清源方联合ADT能控制去势抵抗性前列腺癌荷瘤小鼠的肿瘤生长,与AR/AR-V7信号通路的调控有关。Objective: To explore the efficacy and mechanism of Guben Qingyuan prescription combined with androgen deprivation therapy(ADT)in the treatment of castration-resistant prostate cancer(CRPC). Method: A CRPC-bearing mouse model was established. When the tumor volume reached about 100 mm3,50 CRPC-bearing BALB/c nude mice were randomly divided into the model group,ADT group,and ADT+low-,medium-,high-dose Guben Qingyuan prescription groups,with 10 mice in each group. After grouping,it was ensured that there was no statistically significant difference in tumor volume between groups.The mice in the model group was treated with the same amount of normal saline(10 mL·kg^(-1))by gavage,twice a day, while those in the other groups were provided with bicalutamide(5 mg·kg^(-1)) for intragastric administration,once a day,and then with goserelin(0.36 mg·kg^(-1))for intraperitoneal injection on the 10 th day.On the basis of ADT,the ones in the ADT+Guben Qingyuan prescription groups further received Guben Qingyuan prescription at the low(2.5 g·kg^(-1)),medium(25 g·kg^(-1)),and high doses(50 g·kg^(-1))by gavage,twice a day. After 25 days of continuous administration,the tumor tissue was harvested for recording the tumor growth and calculating the tumor inhibition rate. The mRNA and protein expression levels of androgen receptor(AR),androgen receptor splice variant-7(AR-V7),and prostate-specific antigen(PSA)were detected by realtime polymerase chain reaction(Real-time PCR)and Western blot assay. Result: The tumor inhibition rates of the ADT+low-,medium-,and high-dose Guben Qingyuan prescription groups were 27.95%,46.71%,and44.46%,respectively,and the inhibition rates in the ADT+medium-and high-dose Guben Qingyuan prescription groups were significantly increased as compared with that in the ADT group(P<0.05). As revealed by comparison with the ADT group,Guben Qingyuan prescription at the medium and high doses significantly downregulated the mRNA and protein expression levels of AR,AR-V7,and PSA(P<0.05). Conclusion: Guben Qingy

关 键 词：去势抵抗性前列腺癌(CRPC) 荷瘤小鼠 雄激素受体(AR)信号通路 雄激素受体剪接变异体-7(AR-V7) 固本清源方 

分 类 号：R22[医药卫生—中医基础理论] R242[医药卫生—中医学]