Inhibition of the signal transducer and activator of transcription 3 signaling pathway by Qianliening capsules suppresses the growth and induces the apoptosis of human prostate cells.
The signal transducer and activator of transcription 3 (STAT3) pathway is one of the main growth factor‑mediated signal transduction pathways and is closely associated with the occurrence and development of benign prostatic hyperplasia (BPH). Qianliening capsules (QC) have significant therapeutic effects on BPH; however, the precise mechanism underlying its anti‑BPH activity remains to be elucidated. To further elucidate the molecular mechanism of the therapeutic effect of QC on BPH, the present study used epidermal growth factor (EGF), which has a role in the pathogenesis of BPH, to stimulate the growth of human prostate WPMY‑1 cells and activate the STAT3 pathway in the WPMY‑1 cells. The cell viability was determined using an MTT assay and the cell morphology was observed by phase‑contrast microscopy. Fluorescence activated cell sorting analysis with Annexin‑V/propidium iodide (PI) staining and PI staining were performed to examine cell apoptosis and the cell cycle. The activation of caspase‑9 and ‑3 were evaluated by colorimetric assay. STAT3 phosphorylation and transcriptional activity were detected by western blot analysis and the luciferase gene reporter, respectively. The mRNA and protein expression levels of B‑cell lymhoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), cyclin D1, cyclin‑dependent kinase 4 (CDK4) and p21 were measured by reverse transcription quantitative polymerase chain reaction and western blot analysis, respectively. In the present study, QC was found to significantly and dose‑dependently inhibit the EGF‑stimulated growth of WPMY‑1 cells, as evidenced by QC‑induced cell -morphological changes and a reduction in cell viability. In addition, QC treatment markedly induced the activation of caspase‑9 and ‑3. QC treatment also inhibited the EGF‑mediated increase of STAT3 phosphorylation levels and transcriptional activity in WPMY‑19 cells, accompanied by downregulation of the expression of Bcl‑2, cyclin D1 and CDK4 and upregulation of the expression of Bax and p21. These results suggested that QC effectively inhibited the proliferation and promoted the apoptosis of human prostate cells via modulation of the STAT3 signaling pathway and its target genes, which is likely to be one of the mechanisms underlying its activity in BPH treatment.
Academy of Integrative Medicine Biomedical Research Center, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
Jiumao
J
Lin
Department of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
Jianheng
J
Zhou
Academy of Integrative Medicine Biomedical Research Center, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
Xiaoyong
X
Zhong
Academy of Integrative Medicine Biomedical Research Center, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
Zhenfeng
Z
Hong
Academy of Integrative Medicine Biomedical Research Center, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
Jun
J
Peng
D017209:Apoptosis / Q000187:drug effects*; D002214:Capsules; D053453:Caspase 9 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011467:Prostate / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D002214:Capsules; D004365:Drugs, Chinese Herbal; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; D051028:bcl-2-Associated X Protein; C579120:qianliening; D019938:Cyclin D1; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D053453:Caspase 9