Effects of low-dose bufalin combined with hydroxycamptothecin on human castration-resistant prostate cancer xenografts in nude mice.

Prostate cancer is the most prevalent tumor found in men worldwide. Despite the efficiency of primary endocrine prostate cancer therapies, more efficient drugs are needed to tackle the most advanced and resistant forms of this condition. The present study investigated the antitumor effects of low-dose bufalin combined with hydroxycamptothecin on castration-resistant prostate cancer (CRPC) in mice, as well as the possible mechanisms of apoptosis induction. CRPC xenograft tumors were generated in mice and, subsequently, mice received appropriate doses of bufalin, hydroxycamptothecin or a combination of the two drugs. Tumors from each treatment group were removed, and the tumor volume, weight and inhibition rate of each group was determined. Hematoxylin and eosin staining was performed for pathological analysis and TUNEL staining was used to assess the level of apoptosis in the xenografts. Immunohistochemistry was used for the analysis of proliferating cell nuclear antigen expression and the expression of Bax, Bcl-XL, p53, programmed cell death 4 (PDCD4), phosphorylated (p)-AKT and glycogen synthase kinase (GSK)-3ß was determined by western blotting. Treatment with bufalin significantly (P<0.05) reduced tumor volumes compared with the negative control group, reducing tumor volumes to lower levels when combined with hydroxycampothecin. The combination of bufalin (0.6 or 0.8 mg/kg) and hydroxycampothecin significantly (P<0.05) induced higher levels of cell apoptosis compared with the administration of bufalin or hydroxycampothecin alone. The combination of bufalin and hydroxycampothecin also increased the expression of apoptosis-related proteins Bax, p53, PDCD4 and GSK-3ß, and decreased the expression of Bcl-XL and p-AKT compared with a single drug treatment. The present study suggested that the combination of bufalin and hydroxycampothecin improved the inhibitory effects of both drugs on CRPC tumors in vivo, potentially via the regulation of the PI3K/AKT/GSK-3ß and p53-dependent apoptosis signaling pathways.

Emodin-induced autophagic cell death hinders epithelial-mesenchymal transition via regulation of BMP-7/TGF-ß1 in renal fibrosis.

We aim to explore the effects of emodin and its mechanisms on renal fibrosis (RF). We firstly modeled adriamycin-induced rat RF with unilateral nephrectomy. In vivo and in vitro pharmacological experiments were performed in this study. The presence of collagen deposition was detected by Masson staining. To verify whether emodin attenuates RF by monitoring autophagy, the immunohistochemistry staining for autophagy protein LC3B was performed. We conducted western blot to detect the expression of the autophagy-related proteins in EMT in vitro model after treating with emotin and BMP-7. In vivo, we demonstrated that emodin could improve renal dysfunction and decrease pathological damage of the kidney by activation of autophagy and inhibition of EMT. Upregulation of BMP-7 was recorded in the RF rats subjected to emodin treatment. In vitro studies, emodin has the capacity of reversing EMT and activating autophagy, and emodin could regulate the expression of BMP-7. The results revealed that the attenuation of EMT by emodin could be blocked after the inhibition of BMP-7 and suppression of autophagy. Our findings demonstrated that emodin alleviates EMT during RF by actuating autophagy through BMP-7, suggesting a role of BMP-7 in RF treatment and prevention.

miR-96 regulates migration and invasion of bladder cancer through epithelial-mesenchymal transition in response to transforming growth factor-ß1.

Bladder cancer (BC) is one of the most frequent urological malignancies, and its molecular mechanism still remains unclear. Recent studies have revealed that MicroRNA (miRNAs) acted as oncogenes or tumor suppressors in a variety of cancers. MiRNA-96 has been reported to play a significant role in the development and progression of many cancers. In the current study, we found that transforming growth factor (TGF)-ß1 played a significant role in the progression that miR-96 conducted. And TGF-ß1 could also regulate the expression of FOXQ1, which is the target gene of miR-96. Furthermore, miR-96 induced epithelial-mesenchymal transition in BC cells, which is driven by TGF-ß1. In conclusion, our data revealed that miR-96 regulates the progression and epithelial-mesenchymal transition, which is driven by TGF-ß1 in BC cells; it may provide a new thought for the therapy of BC.

[Surgical options for benign prostatic hyperplasia: impact on sexual function and risk factors].

Benign prostatic hyperplasia (BPH) is a common problem among elderly males. Surgical resection of the hyperplastic tissue to relieve urinary tract obstruction remains a major option for the treatment of BPH. Operations, whether open prostatectomy, transurethral resection of the prostate, or transurethral laser resection of the prostate, will inevitably affect the sexual function of the patient. With the increased attention to patients' quality of life, more and more importance is being attached to the changes in post-BPH sexual function. This review covers the sexual function changes induced by different surgical methods and assesses the possible risk factors of BPH surgery.