Sennoside A induces autophagic death of prostate cancer via inactivation of PI3K/AKT/mTOR axis.

Prostate cancer (PC) is the most common malignancy in male reproductive system. Sennoside A (SA) is an anthraquinone active ingredient extracted from Rheum officinale Baill., which exerts anti-tumor activity on different tumors. In the present study, the toxicity of SA on PC3 and DU 145 cells was detected via CCK-8. The effects of SA on growth, apoptosis, and autophagy were determined through CCK-8, Hoechst stain, flow cytometry, western blot, and immunofluorescence examinations. An in vivo experiment was performed in xenografted mice with intraperitoneal introduction of 10 mg/kg SA and validated via TUNEL, immunohistochemistry and western blot. The results showed that SA inhibited the cell viability with a IC50 value of 52.36 and 67.48 µM in DU 145 and PC3 cells respectively, and enhanced the apoptosis of PC3 and DU 145 cells. Additionally, SA elevated the relative LC3B expression, and the relative protein expression of LC3II/LC3I and Beclin-1, but diminished the P62 protein expression. The relative protein level of p-PI3K/PI3K, p-AKT/AKT and p-mTOR/mTOR was reduced with SA treatment, which was verified by the 740 Y-P application. The 740 Y-P treatments also restored the SA-induced the cell viability, apoptosis rate and relative LC3B expression. Meanwhile, SA inhibited the growth of PC cell and the relative protein level of PI3K/AKT/mTOR axis in vivo. Taken together, SA regulated the proliferation, apoptosis and autophagy via inactivating the PI3K/AKT/mTOR axis in PC.

Integrated bioinformatics analysis of IFITM1 as a prognostic biomarker and investigation of its immunological role in prostate adenocarcinoma.

Introduction: Prostate adenocarcinoma (PRAD) is a highly aggressive malignancy with high mortality and poor prognosis, and its potential mechanism remains unclear. Our study aimed to identify novel markers for the prognosis of PRAD using bioinformatics technology. Methods: The GSE32571 dataset was downloaded from the GEO database, and analyzed via the limma R package to identify differentially expressed genes (DEGs) and differentially expressed immune score-related genes (DEISRGs). The immune-related genes (IRGs) were further obtained by overlapping DEISRGs and DEGs, and the core gene was identified via survival analysis. Furthermore, the expression level, prognostic value, and potential functions of the core gene were evaluated via multiple bioinformatics databases. Results: A total of 301 IRGs were identified from the GSE32571 dataset, and IFITM1 was a down-regulated gene in several types of cancer, including PRAD. Besides, low expression of IFITM1 was associated with a poor prognosis in PRAD. GSEA indicated that the vital pathways of IFITM1-associated genes were mainly enriched in primary immunodeficiency, Th17 cell differentiation, Th1, and Th2 cell differentiation, natural killer cell-mediated cytotoxicity, myeloid dendritic cell activation, regulation of leukocyte activation, etc. Furthermore, IFITM1 was closely correlated with 22 types of tumor-infiltrating immune cells. Discussion: IFITM1 was a prognostic biomarker for PRAD patients, and it can be acted as a potential immune therapy target in PRAD.

MLF1 interacting protein: a potential gene therapy target for human prostate cancer?

Here, we investigated the role of one gene that has been previously associated with human prostate carcinoma cells-myelodysplasia/myeloid leukemia factor 1 interacting protein (MLF1IP)-in order to better ascertain its role in human prostate carcinogenesis. The prostate cancer cell line PC-3 was lentivirally transfected to silence endogenous MLF1IP gene expression, which was confirmed by real-time quantitative PCR (RT-qPCR). Cellomics ArrayScan VTI imaging and MTT assays were conducted to assess cell proliferation. Cell cycle phase arrest and apoptosis were assayed by flow cytometry. Colony formation was assessed by fluorescence microscopy. MLF1IP gene expression was also analyzed by RT-qPCR in sixteen prostate cancer tissue samples and six healthy control prostate tissue samples from human patients. Cell proliferation was significantly inhibited in MLF1IP-silenced cells relative to control cells. G1 phase, S and G2/M phase cell counts were not significantly changed in MLF1IP-silenced cells relative to control cells. Apoptosis was significantly increased in MLF1IP-silenced cells, while MLF1IP-silenced cells displayed a significantly reduced number of cell colonies, compared to control cells. The 16 human prostate cancer tissue samples revealed no clear upregulation or downregulation in MLF1IP gene expression. MLF1IP significantly promotes prostate cancer cell proliferation and colony formation and significantly inhibits apoptosis without affecting cell cycle phase arrest. Further study is required to conclusively determine whether MLF1IP is upregulated in human prostate cancer tumors and to determine the precise cellular mechanism(s) for MLF1IP in prostate carcinogenesis.