Antitumoral effects of 9-cis retinoic acid in adrenocortical cancer

被引：29

作者：

Szabo, Diana Rita ^{[1
]}

Baghy, Kornelia ^{[2
]}

Szabo, Peter M. ^{[3
,4
]}

Zsippai, Adrienn ^{[1
]}

Marczell, Istvan ^{[1
]}

Nagy, Zoltan ^{[1
]}

Varga, Vivien ^{[1
]}

Eder, Katalin ^{[5
]}

Toth, Sara ^{[5
]}

Buzas, Edit I. ^{[5
]}

Falus, Andras ^{[5
]}

Kovalszky, Ilona ^{[2
]}

Patocs, Attila ^{[3
,4
]}

Racz, Karoly ^{[1
]}

Igaz, Peter ^{[1
]}

机构：

[1] Semmelweis Univ, Fac Med, Dept Med 2, H-1088 Budapest, Hungary

[2] Semmelweis Univ, Fac Med, Dept Pathol & Expt Canc Res 1, H-1088 Budapest, Hungary

[3] Hungarian Acad Sci, Mol Med Res Grp, H-1088 Budapest, Hungary

[4] Semmelweis Univ, H-1088 Budapest, Hungary

[5] Semmelweis Univ, Fac Med, Dept Genet Cell & Immunobiol, H-1089 Budapest, Hungary

来源：

CELLULAR AND MOLECULAR LIFE SCIENCES | 2014年 / 71卷 / 05期

基金：

匈牙利科学研究基金会;

关键词：

Adrenocortical cancer; 9-cis retinoic acid; Hormone production; Microarray; Xenograft; Tumor growth; X-RECEPTOR ALPHA; GENE-EXPRESSION; HEPATOCELLULAR-CARCINOMA; 9-CIS-RETINOIC ACID; CELL-LINE; MOLECULAR CLASSIFICATION; GROWTH-INHIBITION; CRITICAL TARGET; BREAST-CANCER; TUMORS;

D O I：

10.1007/s00018-013-1408-z

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

The currently available medical treatment options of adrenocortical cancer (ACC) are limited. In our previous meta-analysis of adrenocortical tumor genomics data, ACC was associated with reduced retinoic acid production and retinoid X receptor-mediated signaling. Our objective has been to study the potential antitumoral effects of 9-cis retinoic acid (9-cisRA) on the ACC cell line NCI-H295R and in a xenograft model. Cell proliferation, hormone secretion, and gene expression have been studied in the NCI-H295R cell line. A complex bioinformatics approach involving pathway and network analysis has been performed. Selected genes have been validated by real-time qRT-PCR. Athymic nude mice xenografted with NCI-H295R have been used in a pilot in vivo xenograft model. 9-cisRA significantly decreased cell viability and steroid hormone secretion in a concentration- and time-dependent manner in the NCI-H295R cell line. Four major molecular pathways have been identified by the analysis of gene expression data. Ten genes have been successfully validated involved in: (1) steroid hormone secretion (HSD3B1, HSD3B2), (2) retinoic acid signaling (ABCA1, ABCG1, HMGCR), (3) cell-cycle damage (GADD45A, CCNE2, UHRF1), and the (4) immune response (MAP2K6, IL1R2). 9-cisRA appears to directly regulate the cell cycle by network analysis. 9-cisRA also reduced tumor growth in the in vivo xenograft model. In conclusion, 9-cisRA might represent a promising new candidate in the treatment of hormone-secreting adrenal tumors and adrenocortical cancer.

引用

页码：917 / 932

页数：16

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