| The incidence of prostate cancer in China is lower than western countries,but in recent years,with the aging of the population and the changes of diet structure,the incidence and mortality rate is gradually rising,it has become the second most common urinary tumors which behind the bladder cancer.Astaxanthin is carotenoid with potent antioxidant,which has many important biological functions.Although many studies have explained the inhibition on cancer cell proliferation,apoptosis and metastasis.The research of astaxanthin on prostate cancer cell and xenograft model is poorly understood,and its mechanism is still unknown.In this study,we investigated the effects of astaxanthin on copper induced RWPE-1 and PC-3 cell endogenous damage,focusing on cell viability,apoptosis,ROS and MDA accumulation,MMP level and antioxidant enzyme system.The results showed that astaxanthin could promote the proliferation on copper ion injured RWPE-1 cell,protect RWPE-1 and PC-3 from endogenous ROS,MDA accumulation and MMP decreasing which induced by copper ion.SOD,CAT and GSH-Px constitute the antioxidant system of cell,copper ion significantly reduced the activity of three enzymes,astaxanthin could promote the activity of SOD,CAT and GSH-Px on RWPE-1 cell,but not inhibition of CAT and GSH-Px in PC-3 cell.Construction of exogenous H2O2 induced oxidative stress model of PC-3 cell,exploring the pathway of astaxanthin on regulation of oxidative stress.The results showed that H2O2 significantly increased the levels of ROS in PC-3 cell,treatment of astaxanthin decreased intracellular ROS accumulation,and it was negatively correlated with the concentration of astaxanthin.Astaxanthin could inhibit H2O2 induced Bcl-2/Bax ratio decrease and caspase 3 activation,thereby reducing the rate of apoptosis.Further study found that astaxanthin could activate Nrf2,away from the Keapl,transfer to the nucleus,combined with ARE element and promote the expression of HO-1.Astaxanthin induced upregulation of HO-1 was regulated by upstream ERK and PI3K/Akt pathway.Astaxanthin improved the H2O2 induced cell viability decrease by ERK pathway of MAPK pathway,but not JNK or p38.Studies of differences of community structure and numbers of bacteria in EPS and prostate biopsy in patients with benign prostatic hyperplasia and prostate cancer.The results showed that numbers of Bacteroidetes,Alphaproteobacteria,Firmicutes,Lachnospiraceae,Propionicimonas,Sphingomonas,Ochrobactrum were higher in prostate cancer than BPH in sample of EPS,Sphingomonas was higher in prostate cancer in sample of prostate biopsy.Combined with the results,it was indicated that Sphingomonas plays a key role in the development of prostate cancer.In addition,further study of prostate bacteria in prostate cancer and BPH patients with and without hypertension,the results showed that Sphingomonas number in BPH patients with hypertension was higher than that without hypertension,but there was no significant difference in prostate cancer patients.Established the PC-3 xenograft prostate tumor in nude mice,and astaxanthin intragastric administration intervention experiment was done.After 31 days,high concentration astaxanthin significantly reduced tumor growth compared with model group,the tumor inhibition rate was 39.7%.Astaxanthin significantly reduced protein expression of PCNA and Ki67,promoted activation of cleaved caspase 3 and increased the positive rate of TUNEL.There was no obvious difference in tumor volume,weight,PCNA and Ki67 protein expression,and results of cleaved caspase 3 and TUNEL between low concentration astaxanthin group and model group.The results of mice intestinal microflora showed that Lachnospiraceae,Lactobacillus and Bacteroidales number were higher in high concentration astaxanthin group.In addition,the expression of miR-375 and miR-487b were significantly increased in high concentration astaxanthin treated tumor compared to model group,suggesting that they might act on some tumor suppressor genes to inhibit tumor growth in tumor progression. |
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