| Objective:To explore the clinical effect of Fu Yang Yi Yin Hua Yu Jie Du plus docetaxel in treatment for castration-resistant prostate cancer,and further understand its molecular mechanism of inducing prostate cancer cell apoptosis.Methods:(1)Clinical research:A total of 54 patients were enrolled,all patients were given maximal androgen blockade(Oral bicalutamide 50mg daily,inject LHRH analog goserelin 3.6mg every 4 weeks)as basic treatment.Patients were randomly divided into treatment group and control group.Cases in the treatment group took Fu Yang Yi Yin Hua Yu Jie Du plus docetaxel(21 days for 1 period 75mg/m2 docetaxel chemotherapy plus oral prednisone 5mg bid)for 24 weeks,and cases in the control group were treated with docetaxel(21 days for 1 period 75mg/m2 docetaxel chemotherapy plus oral prednisone 5mg bid).The PSA,Karnofsky,FACT-P score and the symptomatic score of TCM before and after chemotherapy were compared.Relevant data PSA,Serum testosterone,white blood count,hemoglobin,ALT,AST and serum creatinine were collected.Statistical analysis was performed using SPSS19.0.Measurement data using t test,categorical data analysis with chi-square test.(2)Basic research:We used human normalprostate cells WPMY-1,androgen-dependent prostate cancer cell LNCaP and androgen-independent prostate cancer cell PC3 cells were as study objects.The cells were seeded in six-well plates and then treated with different concentrations of traditional chinese medicine.Microscope was used to observe the morphological changes of the cells.The effects were evaluated by CCK-8 assays and and flow cytometry.The expression of PI3K/Akt/Fox01 associated proteins phosphorylation was examined by Western blot.Results:(1)Clinical research:In control group the PSA values was decreased from 25.9±39.3ng/ml at base line to 20.0±21.1ng/ml after 3 months treatment,whereas in the treatment group it decreased from 22.1±33.9ng/ml to 17.9±19.1 ng/ml.Comparison of the two groups' PSA values before treatment and after,the differences were statistically significant(P<0.05).There were no differences between the two groups(P>0.05).After 6 months treatment,the PSA values of the two groups were increased to 23.1±28.4ng/ml and 19.6±23.5ng/ml,respectively.There were no differences between the two groups(P>0.05).The Kamofsky,FACT-P score and the symptomatic score of TCM in the treatment group were improved after 3 months treatment(P<0.05).No significant change of Karnofsky,FACT-P score and the symptomatic score of TCM was found in the control group at 3 and 6 months after treatment.But no difference was found before and after treatment in control group(P>0.05).(2)Basic research:Fu Yang Yi Yin Hua Yu Jie Du decoction can induce G1 arrest and appotosis in prostate cell line.And decreased PI3K/Akt activity in a dose-dependent manner,inhibits FoxOl phosphorylation,activate the transcription of FoxO1.Finally,Fu Yang Yi Yin Hua Yu Jie Du decoction can effects the expression of apoptosis-associated and cell cycle related genesResults(1)Clinical research:Fu Yang Yi Yin Hua Yu Jie Du decoction plus docetaxel can improve life quality and FACT-P score of patients,including emotion,physical function,insomnia,urination difficult,constipation.And,it had no affect on the liver and kidney function and blood routine.The treatment is feasible and effective in the treatment of CRPC and it is worthy of clinical extend.(2)Basic research:Our study indicates that Fu Yang Yi Yin Hua Yu Jie Du decoction plus docetaxel exerts anti-proliferative properties through affecting PI3K/Akt/FoxO1 signal pathway.And it provide theoretic basis for the clinical treatment of CRPC. |
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