Plasmid-based Stat3 siRNA delivered by hydroxyapatite nanoparticles suppresses mouse prostate tumour growth in vivo  

羟基磷灰石纳米粒子携带Si-Star3质粒抑制小鼠前列腺癌生长的体外研究

作　　者：Zuo-Wen Liang Bao-Feng Guo Yang Li Xiao-Jie Li Xin Li Li-Jing Zhao Li-Fang Gao Hao Yu Xue-Jian Zhao Ling Zhang Bao-Xue Yang 

机构地区：[1]Prostate Diseases Prevention and Treatment Research Centre and Department of Pathophysiology, Norman Bethune Medical School, Jilin University, Changchun 130021, China [2]Department of Emergency Medicine, China-Japan Union Hospital of Jilin University, Changchun 130033, China [3]Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing 100191, China

出　　处：《Asian Journal of Andrology》2011年第3期481-486,514,共7页亚洲男性学杂志（英文版）

基　　金：The authors would thank Mr Qiang-Lin Duan for English usage and paper revision.This work was funded by the National Natural Science Foundation of China （No. 30801354, No. 30970791 and No. 30870921）, the Fundamental Research Funds for the Central Universities of China （No. 200810012） and the Jilin Provincial Science ＆ Technology Department, China （No. 20080154）.

摘　　要：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 C57BIJ6 mice. CaCl2-modified hydroxyapatite carrying si-Stat3 plasmids were injected into tumours, and tumour growth and histology were determined. The expression levels of Star3, pTyr-Stat3, Bcl-2, Bax, Caspase3, VEGFand 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, VEGFand cyclin DI 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.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 C57BIJ6 mice. CaCl2-modified hydroxyapatite carrying si-Stat3 plasmids were injected into tumours, and tumour growth and histology were determined. The expression levels of Star3, pTyr-Stat3, Bcl-2, Bax, Caspase3, VEGFand 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, VEGFand cyclin DI 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.

关 键 词：apoptosis HYDROXYAPATITE prostate cancer RNA interference Star3 

分 类 号：R[医药卫生]