Inhibitor of apoptosis protein Livin promotes tumor progression and chemoradioresistance in human anaplastic thyroid cancer.

Anaplastic thyroid cancer (ATC) is characterized by a rapid and aggressive course of progression. Despite significant advances in surgery, radiotherapy and chemotherapy, the disease­specific mortality due to ATC is approximately 100%. New strategies, such as molecular targeted therapies, are imperative for improving survival. Livin, a member of the human inhibitor of apoptosis protein family, has been found to be associated with tumor progression and poor prognosis in various human cancers. The aim of the present study was to evaluate the role of Livin in cancer progression and chemoradioresistance of ATC and to investigate its potential as a therapeutic target. Endogenous Livin expression in the human BHT101 ATC cell line was silenced by Livin­specific small interfering RNA. To assess the impact of Livin on cancer cell behavior in human ATC cells, various methods such as cell invasion, cell viability and cell apoptosis assays were applied. To assess the expression of Livin and the change of apoptosis­related proteins associated with Livin expression, reverse transcription­quantitative PCR and western blotting were performed. Immunohistochemistry was performed to detect Livin protein expression in human ATC tissues. The association between Livin expression and apoptotic/proliferation index was analyzed in human ATC cells. Livin­knockdown suppressed tumor cell invasion; and conversely, it enhanced cell apoptosis, with elevated expression levels of cleaved caspase­3 and ­7 and cleaved PARP. Livin­knockdown enhanced radiation­induced apoptosis, while reducing cell viability following radiotherapy, as well as lenvatinib treatment. In addition, human ATC tissues with high Livin­expression exhibited a high Ki­67 labeling index and low apoptotic index. In summary, these findings indicate the contribution of Livin to tumor progression and chemoradioresistance in ATC.

Expression of PDCD4 and apoptosis inhibitor Livin in triple negative breast cancer tissues and its relationship with prognosis / 重庆医学

Objective To observe and analyze the expression of programmed cell death 4 (PDCD4) gene and apoptosis inhibitor Livin in triple negative breast cancer (TNBC) tissues and its relationship with prognosis.Methods One hundred cases of TNBC tumor tissue,50 cases of adjacent carcinoma tissue,50 cases of normal breast tissue were selected as the research data.The immunohistochemical technique was applied to detect and compare the expression positive rates of PDCD4 and Livin protein in three kinds of tissues.The patients were followed up.The overall survival (OS) and the progression free survival (PFS) were observed and compared.Results The expression positive rate of PDCD4 in TNBC tissue was significantly lower than that in adjacent carcinoma tissue or normal breast tissue,the differences were statistically significant (x2=26.613,32.000,P＜0.05).The expression was correlated with the clinical pathological features of tumor size,lymph node metastasis,clinical stage,axillary lymph node metastasis and cancer embolus (x2=26.936,13.210,22.774,27.463,5.803,P＜0.05);the expression positive rate of Livin protein in TNBC tissue was significantly higher than that in adjacent carcinoma tissue or normal breast tissue and the expression positive rate of Livin protein in adjacent carcinoma tissue was significantly higher than that in normal breast tissue,the differences were statistically significant (x2 =14.614,57.353,19.048,P＜0.05).The expression was correlated with the clinical pathological features of lymph node metastasis,clinical stage,axillary lymph node metastasis and cancer embolus (x2 =10.788,6.160,27.350,8.914,P＜0.05);OS,PFS in the patients with PDCD4 negative expression were significantly lower than those in the patients with PDCD4positive expression.OS,PFS in the patients with Livin positive expression were significantly lower than those in the patients with Livin negative expression,the above differences were statistically significant (x2 =23.931,19.163,22.649,17.213,P＜0.05).OS in the TNBC patients was correlated with age (RR=1.405),clinical stage (RR =2.897),tumor diameter (RR=2.722),axillary lymph node metastasis (RR=2.516),vascular invasion (RR=3.020),PDCD4 Expression (RR=1.752) and Livin expression (RR=2.051) (P＜0.05).PFS in the patients was correlated with clinical stage (RR =2.756),axillary lymph node metastasis (RR =2.437),PDCD4 expression (RR =1.649) and Livin expression (RR=1.804) (P＜0.05).Conclusion The PDCD4 low expression and Livin protein over-expression exist in TNBC tissues.Their abnormal expressions are correlated with the clinicopathological features of tumor and the prognosis of patient,and could be used as the auxiliary indexes in evaluation of progression and prognosis of TNBC.

Silencing the livin gene enhances the cytotoxic effects of anticancer drugs on colon cancer cells.

PURPOSE: Livin is associated with drug response in several cancers. The aim of this study was to investigate the effect of silencing the livin gene expression on anticancer drug response in colorectal cancer. METHODS: siRNA was transfected at different concentrations (0, 10, and 30nM) into HCT116 cells, then cells were treated with either 5-fluorouracil (FU)/leucovorin (LV) or oxaliplatin (L-OHP)/5-FU/LV. Cellular viability and apoptosis were evaluated following silencing of livin gene expression combined with treatment with anticancer drugs. RESULTS: Livin gene expression was effectively suppressed by 30nM siRNA compared with control and 10nM siRNA. The 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay showed that proliferation was effectively inhibited in cells treated with a combination of both siRNA and an anticancer drug, compared to cells treated with siRNA-Livin or anticancer drug alone. In particular, the combination of 30nM siRNA and L-OHP/5-FU/LV resulted in a 93.8% and 91.4% decrease, compared to untreated control or L-OHP/5-FU/LV alone, respectively. Cellular proliferation was most effectively suppressed by a combination of 30nM of siRNA and L-OHP/5-FU/LV compared to other combinations. CONCLUSION: siRNA-mediated down-regulation of livin gene expression could significantly suppress colon cancer growth and enhance the cytotoxic effects of anticancer drugs such as 5-FU and L-OHP. The results of this study suggest that silencing livin gene expression in combination with treatment with anticancer drugs might be a novel cancer therapy for colorectal cancer.

Silencing the livin gene enhances the cytotoxic effects of anticancer drugs on colon cancer cells

PURPOSE: Livin is associated with drug response in several cancers. The aim of this study was to investigate the effect of silencing the livin gene expression on anticancer drug response in colorectal cancer. METHODS: siRNA was transfected at different concentrations (0, 10, and 30nM) into HCT116 cells, then cells were treated with either 5-fluorouracil (FU)/leucovorin (LV) or oxaliplatin (L-OHP)/5-FU/LV. Cellular viability and apoptosis were evaluated following silencing of livin gene expression combined with treatment with anticancer drugs. RESULTS: Livin gene expression was effectively suppressed by 30nM siRNA compared with control and 10nM siRNA. The 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay showed that proliferation was effectively inhibited in cells treated with a combination of both siRNA and an anticancer drug, compared to cells treated with siRNA-Livin or anticancer drug alone. In particular, the combination of 30nM siRNA and L-OHP/5-FU/LV resulted in a 93.8% and 91.4% decrease, compared to untreated control or L-OHP/5-FU/LV alone, respectively. Cellular proliferation was most effectively suppressed by a combination of 30nM of siRNA and L-OHP/5-FU/LV compared to other combinations. CONCLUSION: siRNA-mediated down-regulation of livin gene expression could significantly suppress colon cancer growth and enhance the cytotoxic effects of anticancer drugs such as 5-FU and L-OHP. The results of this study suggest that silencing livin gene expression in combination with treatment with anticancer drugs might be a novel cancer therapy for colorectal cancer.

Expression of Livin and the inhibition of tumor progression by Livin silencing in laryngohypopharyngeal cancer.

AIM: To evaluate the expression of Livin in human laryngohypopharyngeal squamous cell carcinoma (LHSCC) and investigate whether Livin-knockdown using small interfering-RNA (siRNA) affects tumor aggressiveness in LHSCC cells. MATERIALS AND METHODS: Immunohistochemistry, reverse transcription-polymerase chain reaction, western blotting, cell invasion assay, cell migration assay, and cell apoptosis assays were performed to assess the impact of Livin on cancer cell behavior in human LHSCC. RESULTS: High immunoreactivity of Livin was observed in 22 (36.7%) of the 60 LHSCC tissues relative to adjacent normal mucosa. In the positive-Livin expression group, distant metastasis tended to occur frequently, but the difference was not statistically significant (p=0.06). Livin-knockdown by siRNA induced cell apoptosis through activation of caspase 3, caspase 7, and poly ADP ribose polymerase in LHSCC cells. Livin-knockdown also resulted in significantly reduced cell invasion and migration in LHSCC cells. CONCLUSION: siRNA-mediated silencing of Livin may be associated with the reversal of invasive capacity in LHSCC.

Detection of apoptotic inhibitor protein Livin in different esophageal carcinoma tissue / 中国综合临床

Objective To detect the expression of apoptotic inhibitor protein Livin in different esophageal epithelial lesions and to analyze the relation between the expression of Livin with pathologic characteristics. Methods The expressions of Livin mRNA and Livin protein were detected by real- time fluorescence quantitative PCR and western blot in 40 patients with different esophageal epithelial lesions including normal, atypical hyperplasia, carcino-ma in stiu and invasive carcinoma. Results The expressions of Livin mRNA were progressively increased from nor-mal to invasive carcinoma( 1.00 ± 0. 00,2.26 ± 0.79,7.24 ± 1.06,12.21 ± 2.47 ). There was statistical signifi-cance in Livin mRNA expression among carcinoma in stiu and invasive carcinoma and normal tissues ( P < 0.05 ). Conclusion The expression of Livin is significantly related to the progression of esophageal cancer,which may be a new target for diagnosis and gene treatment of esophageal carcinoma.