Research: SZABÓ and COLLEAGUES,

Listed in Issue 248

Abstract

SZABÓ and COLLEAGUES,  (1)2nd Department of Medicine, Faculty of Medicine, Semmelweis University, Szentkirályi Str. 46, Budapest, 1088, Hungary studied the potential antitumoral effects of 9-cis retinoic acid (9-cisRA) in athymic nude mice to study treatment options of adrenocortical cancer (ACC).

Background

The currently available medical treatment options of adrenocortical cancer (ACC) are limited. In the authors’ previous meta-analysis of adrenocortical tumor genomics data, ACC was associated with reduced retinoic acid production and retinoid X receptor-mediated signalling.

Methodology

The authors’ 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.

Results

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 signalling (ABCA1, ABCG1, HMGCR), (3) cell-cycle damage (GADD45A, CCNE2, UHRF1), and the (4) immune response (MAP2K6, IL1R2).

Conclusion

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.

References

Szabó DR(1), Baghy K, Szabó PM, Zsippai A, Marczell I, Nagy Z, Varga V, Éder K, Tóth S, Buzás EI, Falus A, Kovalszky I, Patócs A, Rácz K, Igaz P. Antitumoral effects of 9-cis retinoic acid in adrenocortical cancer.  Cell Mol Life Sci.71(5):917-32. Mar 2014 doi: 10.1007/s00018-013-1408-z. Epub Jun 27 2013.

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