LAUSR

e14056 Background: Agomelatine is a melatonin receptor agonist (MT1 and MT2) and a 5-HT2C receptor antagonist. Melatonin is a lipophilic compound that is capable of binding to cell surface receptors, cytosolic sites (calmodulin), and directly to nuclear DNA binding sites (nuclear receptors RZR/RORα). Its direct antioxidant, antimitotic, antiestrogenic, prodifferentiating and antimetastatic effects have been well characterized. Nitric oxide (NO) is an inorganic free radical gas synthesized from L-arginine by a family of isoenzymes called NO synthases. Two of these are constitutively expressed and a third is inducible by immunological stimules. The NO released by the constitutive enzymes acts as an important signaling molecule in the cardiovascular and nervous systems and NO released by the inducible NO synthase (iNOS) is generated for long periods, by cells of the immune system among others, and has been shown to be cytostatic/cytotoxic for tumor cells and a variety of microorganisms. Methods: We have studied oncostatic/citostatic influence by ATP-TCA method of agomelatine and agomelatine + trastuzumab solution on the cellular cultures Her2/neu (+), MT1 and MT2 receptor (+) mammary ductal adenocarcinoma (17 cases). Data of ATP-TCA test in healthy patients breast’s cellular cultures with only trastuzumab were used as control. In parallel, we have studied expression of enzyme universal nitric oxide synthase (u-NOS) in cellular cultures of mammary ductal adenocarcinoma all three cells lines using Western blot method. The findings were compared to the data of u-NOS expression in healthy patients breast’s breast cellular cultures. Results: The study demonstrated that influence of citostatic effect of only agomelatine by ATP-TCA method are increased by 32.5% and citostatic effect of agomelatine + trastuzumab by ATP-TCA method also are increased by 45% in compared to control. Expression of universal nitric oxide synthase (u-NOS) is increased in case of mammary ductal adenocarcinoma by 14.2% in case only agomelatine and by 26.7% in case agomelatin + trastuzumab compared to control. Conclusions: Results of this research describe the positive role of agonists melatonin receptors (agomelatin) in the treatment previously treated and after progressed breast cancer (while this mechanism in details is unknown for us) and increased expression of NOS indicate the possibly augmentation sensitivity the cells lines for the citostatics medicines.