Inhibition of growth and angiogenesis of U251 cell xenograft in vivo by short hairpin RNA targeting survivin gene.
- Author:
Hai-ning ZHEN
1
;
Xiang ZHANG
;
Chang-hong SHI
;
Tong-tao YANG
;
Luo-an FU
;
Wei ZHANG
;
Xi-ling WANG
;
Da-kuan GAO
;
Shi-jie HU
;
Lei SONG
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Apoptosis; Brain Neoplasms; metabolism; pathology; Cell Line, Tumor; Female; Glioblastoma; metabolism; pathology; Humans; Inhibitor of Apoptosis Proteins; Male; Mice; Mice, Nude; Microtubule-Associated Proteins; biosynthesis; genetics; Neoplasm Transplantation; Neovascularization, Pathologic; pathology; RNA Interference; RNA, Small Interfering; genetics; Repressor Proteins; Transfection
- From: Chinese Journal of Surgery 2006;44(18):1270-1274
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo observe the impact of specific short hairpin RNA (shRNA) targeting survivin gene on tumorigenesis and angiogenesis of human brain glioblastoma U251 cells in vivo of nude mice.
METHODSU251 cells, U251-SR cells transfected stably with shRNA eukaryotic expression vector pWH1-SR targeting survivin gene, and U251-P cells transfected stably with blank pWH1 vector, were inoculated respectively into subcutaneous tissue in flank of 15 nude mice (each group 5 mice), and the tumor growth status was observed and measured. Protein expressions of survivin, proliferating cell nuclear antigen (PCNA) and factor VIII related antigen (F VIII RAg) were investigated by immunohistochemistry SABC method, apoptotic cells were screened by TUNEL method, furthermore proliferative index (PI), apoptotic index (AI) and microvessel density (MVD) were measured respectively in each group of tumor specimens.
RESULTSComparing with those in U251 and U251-P groups, in U251-SR group, the tumorigenesis time delayed, tumor grew slowly, both tumor volume and tumor weight decreased significantly (P < 0.01 for both); Survivin protein expression was down-regulated markedly; PI and MVD decreased significantly, whereas AI increased remarkably (P < 0.01 for all).
CONCLUSIONSThe specific shRNA targeting survivin gene can inhibit significantly tumorigenesis and angiogenesis of U251 cells in vivo.