RRC ID 51712
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.
Journal Gynecol Oncol
Abstract 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.
Volume 141(3)
Pages 564-569
Published 2016-6-1
DOI 10.1016/j.ygyno.2016.04.003
PII S0090-8258(16)30104-4
PMID 27079211
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
IF 4.623
Times Cited 19
Human and Animal Cells HHUA(RCB0658)