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Expression and biological significance of c-FLIP in human hepatocellular carcinomas.

Du X, Bao G, He X, Zhao H, Yu F, Qiao Q, Lu J, Ma Q - J. Exp. Clin. Cancer Res. (2009)

Bottom Line: And doxorubicin showed apparent inhibition on cell proliferations, and induced more apoptosis.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, PR China. tdsurg@fmmu.edu.cn

ABSTRACT

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.

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Recurrence-free survival in relation to c-FLIP expression. Increased c-FLIP immunoreactivity (c-FLIP overexpression) was associated with shortened survival (Kaplan-Meier curves).
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Figure 2: Recurrence-free survival in relation to c-FLIP expression. Increased c-FLIP immunoreactivity (c-FLIP overexpression) was associated with shortened survival (Kaplan-Meier curves).

Mentions: In univariate analysis, c-FLIP expression was not associated with HCC patient survival (P = 0.204). But c-FLIP overexpression (more than 50%, P = 0.036) implied a lesser probability of survival (Figure. 2). The media recurrence-free survival time for patients with c-FLIP overexpression was 14 months compared with 22 months for those without c-FLIP overexpression.


Expression and biological significance of c-FLIP in human hepatocellular carcinomas.

Du X, Bao G, He X, Zhao H, Yu F, Qiao Q, Lu J, Ma Q - J. Exp. Clin. Cancer Res. (2009)

Recurrence-free survival in relation to c-FLIP expression. Increased c-FLIP immunoreactivity (c-FLIP overexpression) was associated with shortened survival (Kaplan-Meier curves).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2654864&req=5

Figure 2: Recurrence-free survival in relation to c-FLIP expression. Increased c-FLIP immunoreactivity (c-FLIP overexpression) was associated with shortened survival (Kaplan-Meier curves).
Mentions: In univariate analysis, c-FLIP expression was not associated with HCC patient survival (P = 0.204). But c-FLIP overexpression (more than 50%, P = 0.036) implied a lesser probability of survival (Figure. 2). The media recurrence-free survival time for patients with c-FLIP overexpression was 14 months compared with 22 months for those without c-FLIP overexpression.

Bottom Line: And doxorubicin showed apparent inhibition on cell proliferations, and induced more apoptosis.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, PR China. tdsurg@fmmu.edu.cn

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus