Document Detail

Survivin gene RNA interference inhibits proliferation, induces apoptosis, and enhances radiosensitivity in HeLa cells.
MedLine Citation:
PMID:  17098350     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Survivin is a new member of the inhibitors of apoptosis (IAPs) family. It is upregulated in various malignancies including human cervical carcinomas. Reduction of this molecule has resulted in chemosensitization, but it is uncertain whether it can lead to radiosensitization. We observed the effect of survivin gene RNA interference (RNAi) on the proliferation, apoptosis, and radiosensitivity of the human cervical carcinoma cells HeLa. STUDY DESIGN: Human cervical carcinoma cells (HeLa) were transfected with the specific siRNA expression vector (pSilencer2.1-s2) designed to target survivin mRNA. A corresponding site-mutated vector was constructed as a negative control (pSilencer2.1-NC). The expression of survivin mRNA and its protein among the stable transfected cells and the untransfected ones was detected by semi-quantitative RT-PCR and Western blotting respectively. The cell growth was examined by methyl thiazolyl tetrazolium (MTT) assay. The cell cycle distribution and cell apoptosis were measured by flow cytometry. The changes in cell radiosensitivity were observed by clonogenic survival assay. RESULTS: Three stable transfected cell lines: HeLa-s2 (with pSilencer2.1-s2), HeLa-NC (with pSilencer2.1-NC), and HeLa-U6 neo (with empty vector pSilencer2.1-U6 neo) were established. The expression levels of survivin gene mRNA and protein in HeLa-s2 were significantly lower than in HeLa-NC, HeLa-U6 neo, and those untransfected HeLa cells. The expression inhibitory rates were 62.8% and 60.1%. The cell proliferation of HeLa-s2 was inhibited, and the highest inhibitory rate was 57.8+/-2.1%. The changes in cell cycle distribution in HeLa-s2 compared with the other three cell lines were obvious, many cells were blocked in the G(0)/G(1) phase 72.7+/-3.1% (P<0.05), reduced sharply in the G(2)/M phase (5.1+/-2.9)% (P<0.05), and also the apoptotic rate was 29.2+/-1.4%, obviously increasing (P<0.05). At the same dose of radiation, the cloning efficiency of HeLa-s2 declined notably (P<0.05); the cell survival curve showed a significant decrease in D(0) and D(q), which were 3.15 and 1.21, respectively (P<0.05), and the radiation enhancement ratios were 2.01 (a ratio of D(0)) and 1.77 (a ratio of D(q)). CONCLUSIONS: Survivin gene RNAi not only could inhibit the proliferation of human cervical carcinoma cells (HeLa), but also could significantly enhance the radiosensitivity of those cells through the reduction of its mRNA and protein. Therefore, an RNAi-targeted survivin gene strategy would be a potential approach to radiosensitization therapy in human cervical carcinomas.
Hui Song; Xiao-Yan Xin; Feng Xiao; De-Tang Wang; Qiao-Hong Yue; Xing Han
Publication Detail:
Type:  Journal Article     Date:  2006-11-13
Journal Detail:
Title:  European journal of obstetrics, gynecology, and reproductive biology     Volume:  136     ISSN:  0301-2115     ISO Abbreviation:  Eur. J. Obstet. Gynecol. Reprod. Biol.     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2008-01-09     Completed Date:  2008-03-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375672     Medline TA:  Eur J Obstet Gynecol Reprod Biol     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  83-9     Citation Subset:  IM    
Department of Obstetrics and Gynecology, Xijing Hospital, Fourth Military Medical University, Shannxi, Xi'an 710032, China.
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MeSH Terms
Apoptosis / drug effects*
Cell Proliferation / drug effects*
Cell Survival / drug effects
Cysteine Proteinase Inhibitors / genetics*
Gene Expression Regulation, Neoplastic / drug effects
Hela Cells
Microtubule-Associated Proteins / genetics*
Neoplasm Proteins / genetics*
RNA Interference*
RNA, Messenger / biosynthesis
Radiation Tolerance / drug effects*
Uterine Cervical Neoplasms / radiotherapy
Reg. No./Substance:
0/BIRC5 protein, human; 0/Cysteine Proteinase Inhibitors; 0/Microtubule-Associated Proteins; 0/Neoplasm Proteins; 0/RNA, Messenger

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