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Expression and biological significance of c-FLIP in human hepatocellular carcinomas
Xilin Du1, Guoqiang Bao, Xianli He
1Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, PR China. tdsurg@fmmu.edu.cn
Background:
c-FLIP can be considered as a tumor-progression factor in regard to its anti-apoptotic functions. In the present study, we intended to investigate the expression of c-FLIP in human HCC tissues, and its relation with drug-induced cell apoptosis through the specific inhibition of c-FLIP expression by siRNA in 7721 cells.
Methods:
c-FLIP expression was quantified immunohistochemically in HCC tissues(eighty-six cases), and corresponding noncancerous tissues (fifty-seven cases). Patients with HCC were followed up for cancer recurrence. Then, the c-FLIP gene was silenced with specific siRNA in 7721 HCC cells. c-FLIP expression was detected by RT-PCR, Western Blot and immunocytochemical staining. The cellular viability and cell apoptosis were assayed in vitro with cells treated with doxorubicin.
Results:
Positive immunostaining was detected for c-FLIP in 83.72% (72/86) human HCC tissues, 14.81% (4/27) hepatic cirrhosis, 11.11% (2/18) hepatic hemangioma tissues, and absent in normal hepatic tissues. The overexpression(more than 50%) of c-FLIP in HCC adversely affected the recurrence-free survival. Through c-FLIP gene silencing with siRNA, the expressions of c-FLIP mRNA and protein were remarkably down-regulated in 7721 HCC cells. And doxorubicin showed apparent inhibition on cell proliferations, and induced more apoptosis.
Conclusion:
These results indicate that c-FLIP is frequently expressed in human HCCs, and its overexpression implied a lesser probability of recurrence-free survival. The specific silencing of c-FLIP gene can apparently up-regulate drug-induced HCC cell apoptosis, and may have therapeutic potential for the treatment of human HCC.
Insights
Cellular FLIP (c-FLIP) is overexpressed in hepatocellular carcinoma (HCC), correlating with poor survival. Silencing c-FLIP enhances drug-induced apoptosis in HCC cells, suggesting therapeutic potential.
Area of Science:
- Oncology
- Molecular Biology
- Hepatology
Background:
- Cellular FLIP (c-FLIP) exhibits anti-apoptotic functions, potentially acting as a tumor-progression factor.
- Investigating c-FLIP expression in human hepatocellular carcinoma (HCC) is crucial for understanding its role in disease progression.
Purpose of the Study:
- To determine the expression levels of c-FLIP in human HCC tissues.
- To evaluate the relationship between c-FLIP expression and drug-induced apoptosis in HCC cells.
- To explore the therapeutic potential of c-FLIP inhibition in HCC.
Main Methods:
- Immunohistochemistry was used to quantify c-FLIP expression in 86 HCC tissues and 57 noncancerous tissues.
- c-FLIP gene silencing was performed using siRNA in 7721 HCC cells, with expression levels confirmed by RT-PCR and Western Blot.
- Cellular viability and apoptosis were assessed in doxorubicin-treated cells following c-FLIP gene silencing.
Main Results:
- c-FLIP was expressed in 83.72% of HCC tissues, with higher expression linked to adverse recurrence-free survival.
- siRNA-mediated c-FLIP silencing significantly reduced c-FLIP mRNA and protein levels in HCC cells.
- Doxorubicin treatment induced greater apoptosis and inhibited proliferation in HCC cells with silenced c-FLIP.
Conclusions:
- c-FLIP is frequently overexpressed in human HCC and associated with a higher recurrence rate.
- Specific silencing of c-FLIP enhances drug-induced apoptosis in HCC cells.
- Targeting c-FLIP presents a potential therapeutic strategy for human HCC treatment.
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