Exploration of Mechanism of Guben Qingyuan Prescription Combined with Androgen Deprivation Therapy Against Castration-resistant Prostate Cancer from AR/AR-V7 Signaling Pathway
10.13422/j.cnki.syfjx.20211599
- VernacularTitle: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
- Author:
Hao-ran CHEN
1
;
Su-ping FANG
1
;
Di ZHANG
1
;
Jia-zheng WANG
1
;
Hao LIU
1
Author Information
1. Guang'anmen Hospital， China Academy of Chinese Medical Sciences，Beijing 100053，China
- Publication Type:Research Article
- Keywords:
castration resistant prostate cancer （CRPC）;
tumor-bearing mice;
androgen receptor （AR） signaling pathway;
androgen receptor splice variant 7 （AR-V7）;
Guben Qingyuan prescription
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2021;27(15):16-21
- CountryChina
- Language:Chinese
-
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 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 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 （P<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 （P<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.
