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

Hao-ran CHEN; Su-ping FANG; Di ZHANG; Jia-zheng WANG; Hao LIU

doi:10.13422/j.cnki.syfjx.20211599

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

Pharmacology | 更新时间：2021-07-15

- Exploration of Mechanism of Guben Qingyuan Prescription Combined with Androgen Deprivation Therapy Against Castration-resistant Prostate Cancer from AR/AR-V7 Signaling Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 27, Issue 15, Pages: 16-21(2021)
- 作者机构：
  
  中国中医科学院广安门医院，北京 100053
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20211599
  CLC： R22;R242;R285.5;R2-031;R287
- Received：17 March 2021，
  
  Published Online：07 June 2021，
  
  Published：05 August 2021
- 稿件说明：
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陈浩然,方素萍,张迪等.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[J].中国实验方剂学杂志,2021,27(15):16-21.

CHEN Hao-ran,FANG Su-ping,ZHANG Di,et al.Exploration of Mechanism of Guben Qingyuan Prescription Combined with Androgen Deprivation Therapy Against Castration-resistant Prostate Cancer from AR/AR-V7 Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(15):16-21.
陈浩然,方素萍,张迪等.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[J].中国实验方剂学杂志,2021,27(15):16-21. DOI： 10.13422/j.cnki.syfjx.20211599.

CHEN Hao-ran,FANG Su-ping,ZHANG Di,et al.Exploration of Mechanism of Guben Qingyuan Prescription Combined with Androgen Deprivation Therapy Against Castration-resistant Prostate Cancer from AR/AR-V7 Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(15):16-21. DOI： 10.13422/j.cnki.syfjx.20211599.

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 mm

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（

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（

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。

Abstract

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 mm

， 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 10th 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 real-time 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%， and 44.46%， 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 （

0.05）. As revealed by comparison with the ADT group， Guben Qingyuan prescription at the medium and high doses significantly down-regulated the mRNA and protein expression levels of AR， AR-V7， and PSA （

0.05）.

Conclusion

Guben Qingyuan prescription combined with ADT is efficient in controlling the tumor growth in CRPC-bearing mice， which is related to the regulation of AR/AR-V7 signaling pathway.

关键词

Keywords

references

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