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Updated: Jun 4, 2026
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Plasmid-based Stat3 siRNA delivered by hydroxyapatite nanoparticles suppresses mouse prostate tumour growth in vivo
Zuo-Wen Liang1, Bao-Feng Guo, Yang Li
1Prostate Diseases Prevention and Treatment Research Centre and Department of Pathophysiology, Norman Bethune Medical School, Jilin University, Changchun 130021, China.
Abstract:
DNA vector-based Stat3-specific RNA interference (si-Stat3) blocks Stat3 signalling and inhibits prostate tumour growth. However, the antitumour activity depends on the efficient delivery of si-Stat3. The effects on the growth of mouse prostate cancer cells of si-Stat3 delivered by hydroxyapatite were determined in this study. RM-1 tumour blocks were transplanted into C57BL/6 mice. CaCl₂-modified hydroxyapatite carrying si-Stat3 plasmids were injected into tumours, and tumour growth and histology were determined. The expression levels of Stat3, pTyr-Stat3, Bcl-2, Bax, Caspase3, VEGF and cyclin D1 were measured by western blot analysis. Amounts of apoptosis in cancer cells were analysed with immunohistochemistry and the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL) assay. The results showed that hydroxyapatite-delivered si-Stat3 significantly suppressed tumour growth up to 74% (P < 0.01). Stat3 expression was dramatically downregulated in the tumours. The immunohistochemistry and TUNEL results showed that si-Stat3-induced apoptosis (up to 42%, P < 0.01). The Stat3 downstream genes Bcl-2, VEGF and cyclin D1 were also strongly downregulated in the tumour tissues that also displayed significant increases in Bax expression and Caspase3 activity. These results suggest that hydroxyapatite can be used for the in vivo delivery of plasmid-based siRNAs into tumours.
Insights
Hydroxyapatite effectively delivered small interfering RNA targeting Signal transducer and activator of transcription 3 (si-Stat3) to inhibit prostate tumor growth. This novel delivery method significantly increased apoptosis and suppressed key tumor markers.
Area of Science:
- Biomedical Engineering
- Oncology
- Molecular Biology
Background:
- Signal transducer and activator of transcription 3 (Stat3) signaling is crucial for prostate tumor growth.
- Effective delivery of Stat3-specific RNA interference (si-Stat3) is essential for its anti-tumor activity.
- Hydroxyapatite (HA) is explored as a potential delivery vehicle for therapeutic agents.
Purpose of the Study:
- To evaluate the efficacy of hydroxyapatite-mediated delivery of si-Stat3 for inhibiting prostate tumor growth in vivo.
- To investigate the molecular mechanisms underlying the anti-tumor effects of HA-delivered si-Stat3.
Main Methods:
- si-Stat3 plasmids were complexed with CaCl₂-modified hydroxyapatite.
- The HA-si-Stat3 complex was injected into RM-1 prostate tumors in C57BL/6 mice.
- Tumor growth, histology, apoptosis (TUNEL assay, immunohistochemistry), and expression of key proteins (Stat3, pTyr-Stat3, Bcl-2, Bax, Caspase3, VEGF, cyclin D1) were analyzed.
Main Results:
- Hydroxyapatite-delivered si-Stat3 significantly suppressed tumor growth by up to 74% (P < 0.01).
- si-Stat3 treatment dramatically downregulated Stat3 expression and its downstream targets (Bcl-2, VEGF, cyclin D1).
- Apoptosis was significantly increased (up to 42%, P < 0.01), accompanied by increased Bax expression and Caspase3 activity.
Conclusions:
- Hydroxyapatite serves as an effective delivery system for plasmid-based siRNAs in vivo.
- HA-mediated si-Stat3 delivery demonstrates significant anti-prostate tumor efficacy by inducing apoptosis and inhibiting Stat3 signaling.
- This approach holds promise for the development of novel prostate cancer therapies.
