The new platinum-based anticancer agent LA-12 induces retinol binding protein 4 in vivo

Proteome Science

Borivoj Vojtesek⁶  Petr Sova¹  Jiri Damborsky²  Lenka Hernychova⁵  Iva Struharova⁶  Monika Dvorakova⁶  Kristyna Hrazdilova³  Jiri Jarkovsky⁴  Pavel Bouchal⁶ 

[1] Platinum Pharmaceuticals a.s., Karasek 1, 621 33 Brno, Czech Republic;Centre of Biomolecular and Cellular Engineering, International Clinical Research Center, St. Anne's University Hospital Brno, Pekarska 53, 656 91 Brno, Czech Republic;Masaryk Memorial Cancer Institute, Department of Oncological and Experimental Pathology, Zluty kopec 7, 656 53 Brno, Czech Republic;Masaryk University, Institute of Biostatistics and Analyses, Kamenice 3, 625 00 Brno, Czech Republic;University of Defence, Faculty of Military Health Sciences, Institute of Molecular Pathology, Trebesska 1575, 500 03 Hradec Kralove, Czech Republic;Masaryk Memorial Cancer Institute, Regional Centre for Applied Molecular Oncology, Zluty kopec 7, 656 53 Brno, Czech Republic

关键词: proteomics;    adamantylamine;    cisplatin;    RBP4;    plasma retinol-binding protein 4;    (OC-6-43)-bis(acetato)(1-adamantylamine)amminedichloroplatinum (IV) (LA-12);   

Others  :  820127
DOI  :  10.1186/1477-5956-9-68

 received in 2011-05-25, accepted in 2011-10-31,  发布年份 2011

【 摘 要 】

Background

The initial pharmacokinetic study of a new anticancer agent (OC-6-43)-bis(acetato)(1-adamantylamine)amminedichloroplatinum (IV) (LA-12) was complemented by proteomic screening of rat plasma. The objective of the study was to identify new LA-12 target proteins that serve as markers of LA-12 treatment, response and therapy monitoring.

Methods

Proteomic profiles were measured by surface-enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF MS) in 72 samples of rat plasma randomized according to LA-12 dose and time from administration. Correlation of 92 peak clusters with platinum concentration was evaluated using Spearman correlation analysis.

Results

We identified Retinol-binding protein 4 (RBP4) whose level correlated with LA-12 level in treated rats. Similar results were observed in randomly selected patients involved in Phase I clinical trials.

Conclusions

RBP4 induction is in agreement with known RBP4 regulation by amantadine and cisplatin. Since retinol metabolism is disrupted in many cancers and inversely associates with malignancy, these data identify a potential novel mechanism for the action of LA-12 and other similar anti-cancer drugs.

【 授权许可】

   
2011 Bouchal et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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