title: Plasmid-based Stat3 siRNA delivered by hydroxyapatite nanoparticles suppresses mouse prostate tumour growth in vivo.
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.
authors.affiliation: Prostate Diseases Prevention and Treatment Research Centre and Department of Pathophysiology, Norman Bethune Medical School, Jilin University, Changchun 130021, China.
authors.forename: Zuo-Wen
authors.initials: ZW
authors.lastname: Liang
authors.forename: Bao-Feng
authors.initials: BF
authors.lastname: Guo
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Xiao-Jie
authors.initials: XJ
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Li-Jing
authors.initials: LJ
authors.lastname: Zhao
authors.forename: Li-Fang
authors.initials: LF
authors.lastname: Gao
authors.forename: Hao
authors.initials: H
authors.lastname: Yu
authors.forename: Xue-Jian
authors.initials: XJ
authors.lastname: Zhao
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Bao-Xue
authors.initials: BX
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D017886:Durapatite / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles; D010957:Plasmids; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use*
chemical_list: D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D017886:Durapatite