Aim： To investigate the activity of RRR-α-tocopheryloxybutyric acid （TOB）, an ether analog of RRR-α-tocopheryl succinate （VES）, in prostate cancer cells. Methods： VES and TOB were used to treat prostate cancer...Aim： To investigate the activity of RRR-α-tocopheryloxybutyric acid （TOB）, an ether analog of RRR-α-tocopheryl succinate （VES）, in prostate cancer cells. Methods： VES and TOB were used to treat prostate cancer LNCaP, PC3, and 22Rvl cells and primary-cultured prostate fibroblasts. The proliferation rates were determined by MTT assay, the cell viabilities were determined by trypan blue exclusion assay, and the cell deaths were evaluated by using Cell Death Detection ELISA kit. The protein expression levels were determined by Western blot analysis. Results： The MTT growth assay demonstrated that TOB could effectively suppress the proliferation of prostate cancer cells, but not normal prostate fibroblasts. Mechanism dissections revealed that TOB reduced cell viability and induced apoptosis in prostate cancer cells similar to VES. In addition, both TOB and VES suppressed prostate-specific antigen （PSA） at the transcriptional level leading to reduced PSA protein expression. Furthermore, vitamin D receptor （VDR） expression increased after the addition of TOB. Conclusion： Our data suggests that the VES derivative, TOB, is effective in inhibiting prostate cancer cell proliferation, suggesting that TOB could be used for both chemopreventive and chemotherapeutic purposes in the future.展开更多
Prostate cancer(PCa)is the most common malignancy in men.Despite aggressive therapy involving surgery and hormonal treatments,the recurrence and emergence of metastatic castration-resistant prostate cancer(CRPCa)remai...Prostate cancer(PCa)is the most common malignancy in men.Despite aggressive therapy involving surgery and hormonal treatments,the recurrence and emergence of metastatic castration-resistant prostate cancer(CRPCa)remain a major challenge.Dysregulation of the transforming growth factor-β(TGF-β)signaling pathway is crucial to PCa development and progression.This also contributes to androgen receptor activation and the emergence of CRPC.In addition,TGF-β signaling regulates long non-coding RNA(lncRNA)expression in multiple cancers,including PCa.Here,we discuss the complex regulatory network of lncRNAs and TGF-β signaling in PCa and their potential applications in diagnosing,prognosis,and treating PCa.Further investigations on the role of lncRNAs in the TGF-β pathway will help to better understand PCa pathogenesis.展开更多
Objective:To detect the expression of TNF-αand IL-6 in simple benign prostatic hyperplasia(BPH)and BPH combined with prostatitis,and to evaluate the effect of inflammation of the development and progression of BPH.Me...Objective:To detect the expression of TNF-αand IL-6 in simple benign prostatic hyperplasia(BPH)and BPH combined with prostatitis,and to evaluate the effect of inflammation of the development and progression of BPH.Methods:Specimens of 90 patients with BPH underwent transurethral resection of prostate(TURP)were obtained.All speci-mens were divided histologically by HE staining into group of 35 cases of simple BPH(A group)and group of 55 cases of BPH combined with prostatitis(B group).Proteins levels of TNF-αand IL-6 were examined by immunohistochemistry.All patients’clinical indicators including PSA,prostate volume,age,urinary flow rate were recorded,and all patients were diagnosed as BPH by pathology.Results:All patients of B group were found combined with chronic prostatitis.The constituent ratio was 61%.Patients’prostate volume and PSA of B group were significant higher than A group(p<.05),but there were no significant differences in urine flow rate and patients’age(p>.05).As compared with A group,the expression of TNF-αand IL-6 significantly increased in B group(p<.05).The results of analysis were as follows:there existed a moderate correlation between prostate volume and patients’age(r=0.430,p<.001);there existed a moderate correlation between prostate volume and the degree of inflammation(r=0.610 and r=0.609,p<.01);there existed a moderate correlation between PSA and the degree of inflammation(r=0.572 and r=0.487,p<.01);there was not significant correlation between PSA and patients’age(r=0.065,p>.1);controlling influence of the age factor by partial correlation analysis,there was still a significant correlation between the prostate volume and level of inflammation.Conclusions:Most BPH patients are combined with prostatitis especially chronic inflammation.TNF-αand IL-6 are two-pro-inflammation cytokines,which obtain high expression in the prostate tissue combined with histological inflammation.Patients’prostate volume and PSA of BPH combined with prostatitis are significantly higher than those of simple BPH.However,there are no significant differences in urine flow rate and patients’age.These two cytokines may play an important part in promoting BPH and secretion of PSA.展开更多
文摘Aim： To investigate the activity of RRR-α-tocopheryloxybutyric acid （TOB）, an ether analog of RRR-α-tocopheryl succinate （VES）, in prostate cancer cells. Methods： VES and TOB were used to treat prostate cancer LNCaP, PC3, and 22Rvl cells and primary-cultured prostate fibroblasts. The proliferation rates were determined by MTT assay, the cell viabilities were determined by trypan blue exclusion assay, and the cell deaths were evaluated by using Cell Death Detection ELISA kit. The protein expression levels were determined by Western blot analysis. Results： The MTT growth assay demonstrated that TOB could effectively suppress the proliferation of prostate cancer cells, but not normal prostate fibroblasts. Mechanism dissections revealed that TOB reduced cell viability and induced apoptosis in prostate cancer cells similar to VES. In addition, both TOB and VES suppressed prostate-specific antigen （PSA） at the transcriptional level leading to reduced PSA protein expression. Furthermore, vitamin D receptor （VDR） expression increased after the addition of TOB. Conclusion： Our data suggests that the VES derivative, TOB, is effective in inhibiting prostate cancer cell proliferation, suggesting that TOB could be used for both chemopreventive and chemotherapeutic purposes in the future.
基金supported by intramural funds from BITS Pilani,Hyderabad,India.
文摘Prostate cancer(PCa)is the most common malignancy in men.Despite aggressive therapy involving surgery and hormonal treatments,the recurrence and emergence of metastatic castration-resistant prostate cancer(CRPCa)remain a major challenge.Dysregulation of the transforming growth factor-β(TGF-β)signaling pathway is crucial to PCa development and progression.This also contributes to androgen receptor activation and the emergence of CRPC.In addition,TGF-β signaling regulates long non-coding RNA(lncRNA)expression in multiple cancers,including PCa.Here,we discuss the complex regulatory network of lncRNAs and TGF-β signaling in PCa and their potential applications in diagnosing,prognosis,and treating PCa.Further investigations on the role of lncRNAs in the TGF-β pathway will help to better understand PCa pathogenesis.
文摘Objective:To detect the expression of TNF-αand IL-6 in simple benign prostatic hyperplasia(BPH)and BPH combined with prostatitis,and to evaluate the effect of inflammation of the development and progression of BPH.Methods:Specimens of 90 patients with BPH underwent transurethral resection of prostate(TURP)were obtained.All speci-mens were divided histologically by HE staining into group of 35 cases of simple BPH(A group)and group of 55 cases of BPH combined with prostatitis(B group).Proteins levels of TNF-αand IL-6 were examined by immunohistochemistry.All patients’clinical indicators including PSA,prostate volume,age,urinary flow rate were recorded,and all patients were diagnosed as BPH by pathology.Results:All patients of B group were found combined with chronic prostatitis.The constituent ratio was 61%.Patients’prostate volume and PSA of B group were significant higher than A group(p<.05),but there were no significant differences in urine flow rate and patients’age(p>.05).As compared with A group,the expression of TNF-αand IL-6 significantly increased in B group(p<.05).The results of analysis were as follows:there existed a moderate correlation between prostate volume and patients’age(r=0.430,p<.001);there existed a moderate correlation between prostate volume and the degree of inflammation(r=0.610 and r=0.609,p<.01);there existed a moderate correlation between PSA and the degree of inflammation(r=0.572 and r=0.487,p<.01);there was not significant correlation between PSA and patients’age(r=0.065,p>.1);controlling influence of the age factor by partial correlation analysis,there was still a significant correlation between the prostate volume and level of inflammation.Conclusions:Most BPH patients are combined with prostatitis especially chronic inflammation.TNF-αand IL-6 are two-pro-inflammation cytokines,which obtain high expression in the prostate tissue combined with histological inflammation.Patients’prostate volume and PSA of BPH combined with prostatitis are significantly higher than those of simple BPH.However,there are no significant differences in urine flow rate and patients’age.These two cytokines may play an important part in promoting BPH and secretion of PSA.
