Reference - Detail
|Author||Chuwa AH, Sone K, Oda K, Ikeda Y, Fukuda T, Wada-Hiraike O, Inaba K, Makii C, Takeuchi M, Oki S, Miyasaka A, Kashiyama T, Arimoto T, Kuramoto H, Kawana K, Yano T, Osuga Y, Fujii T.|
|Title||Significance of survivin as a prognostic factor and a therapeutic target in endometrial cancer.|
INTRODUCTION:Survivin is an anti-apoptotic protein encoded by the baculoviral inhibitor of apoptosis repeat-containing (BIRC5) gene and is upregulated in 83% of endometrial cancers. We aimed to elucidate the prognostic importance of BIRC5 expression, and evaluate survivin as a therapeutic target for endometrial cancer, by knock-down of BIRC5 and using the survivin inhibitor-YM155.
METHODS:RNA sequencing data in 234 patients with endometrial carcinoma was obtained from The Cancer Genome Atlas database, and analyzed using Kaplan-Meier method, log-rank test and Cox proportional hazard model. Expressions of survivin in 16 endometrial cancer cell lines were analyzed by western blotting. Knocking down effect on survivin expression was evaluated using a small interfering RNA (siRNA). The anti-proliferative and pro-apoptotic effects of YM155 were assessed with cell viability, flow cytometry, and annexin V/propidium iodide assays.
RESULTS:High expression of BIRC5 was associated with poor progression free survival (P=0.006), and shown to be an independent prognostic factor (HR=1.97, 95% CI=1.29-4.5, P=0.045). Survivin was upregulated in 14 of 16 (87.5%) endometrial cancer cell lines, compared with endometrial immortalized cells. Apoptosis was induced by knockdown of BIRC5 in all 3 cell lines examined. YM155 showed increased population of sub-G1 cells (P<0.001) in all 16 cell lines, and IC50 values to YM155 were <50nm in 15 cell lines. YM155 dose-dependently and significantly increased the apoptotic cell population in all 16 cell lines (P<0.001).
CONCLUSIONS:Present study indicated that survivin expression is a significant prognostic factor and that survivin is a promising therapeutic target for endometrial cancer.
|MeSH||Antineoplastic Agents / pharmacology Apoptosis / drug effects Biomarkers, Tumor / antagonists & inhibitors Biomarkers, Tumor / biosynthesis Biomarkers, Tumor / genetics Cell Line, Tumor Cell Proliferation / drug effects Disease-Free Survival Endometrial Neoplasms / drug therapy* Endometrial Neoplasms / genetics Endometrial Neoplasms / metabolism* Endometrial Neoplasms / pathology Female Humans Imidazoles / pharmacology Inhibitor of Apoptosis Proteins / antagonists & inhibitors* Inhibitor of Apoptosis Proteins / biosynthesis* Inhibitor of Apoptosis Proteins / genetics Middle Aged Molecular Targeted Therapy Naphthoquinones / pharmacology Prognosis Survivin|
|Human and Animal Cells||HHUA(RCB0658)|