[Expression of livin in gastric cancer and effect of silencing of the livin gene on apoptosis in gastric cancer cells].
OBJECTIVE
The aim of this study was to detect the expression of livin in human gastric carcinoma and analyze the relationship between livin expression and cliniopathologic features. To explore the feasibility of small interference RNA (siRNA) in inhibition of livin gene expression and to investigate the apoptosis susceptibility of SGC-7901 cells by siRNA-mediated silencing of the livin gene.


METHODS
The expression of livin at mRNA and protein levels were determined by RT-PCR and Western blot assay, respectively. The relationship between livin expression and clinicopathologic features was analyzed. Two siRNAs specifically targeting livin gene were designed and synthesized in vitro, and were transfected into the gastric cancer SGC-7901 cells. The expression of livin mRNA was assayed by RT-PCR. Cell growth state and 50% inhibition concentration (IC50) of 5-Fu and cisplatin on SGC-7901 cells were determined by MTT method. Cell apoptosis was assessed by flow cytometry (FCM).


RESULTS
The expressions of livin mRNA and protein were detected in 19 of 40 gastric carcinoma cases (47.5%). No expression of livin was detected in tumor-adjacent tissues and benign gastric lesion. A positive correlation was found between livin expression and poor differentiation as well as lymph node metastases (P < 0.05). The level of livin mRNA was decreased in the SGC-7901 cells transfected by si-livin1 for 48 hours, with inhibition of cell growth. IC50 of si-livin-treated SGC-7901 cells to 5-Fu and cisplatin was decreased (P < 0.05) and the cells were more susceptible to proapoptotic stimuli (5-Fu and cisplatin) than control groups (P < 0.05).


CONCLUSIONS
Livin is overexpressed in gastric carcinoma with a correlation to tumor differentiation and lymph node metastasis, suggesting that it may be as one of molecular prognostic factors for some cases of gastric cancer. SiRNA can inhibit livin expression of SGC-7901 cells and induce cell apoptosis. Livin might serve as a new target for apoptosis-inducing therapy of gastric cancer. Livin;
Liu
Ping
P
Department of Oncology, the First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China. liupinga28@yahoo.com.cn
Wang
Tong-shan
TS
You
Si-hong
SH
Ge
Hong-Mei
HM
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D008207:Lymphatic Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics*; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; C419866:BIRC7 protein, human; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D002945:Cisplatin; D005472:Fluorouracil