Inhibitory effect of methionine-enkephalin on tumor growth

A metionina-enceflalina (Met-Ehk) é um pentapeptídeo opióide derivado do pró-normônio proencefalina A. presente em células neuroendócrinas e hematopoéticas. Estudos experimentais evidenciam seu papel na indução, ativação e controle de eventos imunomodula-dores, inclusive com potente efeito inibidor do crescimento tumoral. O presente estudo demonstra que o efeito inibidor da Met-Enk no crescimento de um fibro-histiocitoma, em camundongos BALB/cJ, é influenciado pelo protocolo utilizado, via de administração e dose do pentapeptídeo opióide utilizada no tratamento. A administração de Met_Enk por via intracerebral retardou de forma eficiente o processo de tumorigênese, aumentando a sobrevida dos animais e reduzindo de forma significativa a área tumoral final. Dose baixa (0,25 mg/kg) de Met-Enk administrada por via intracerebral foi ainda mais potente no controle da tumorigênese. Methionine-enkephalin (Met-Enk) is an endogenous opioid pentapeptide derived from the prohormone proenkephalin A, present in neuroendocrine and hematopoietic cells. Enkephalins are known to play an important role on the processes of induction, activation and control of immunomodulatory events. Met-Enk has been considered a potent antitumoral agent. The present study shows that Met-Enk exerts an inhibitory effect on the growth of a macrophage derived fibrous histiocytoma (MC-II) inoculated intradermally into BALB/cJ mice. Such effect was mainly influenced by the protocol, route of administration and concentration of Met-Enk used for treatment. Neither higher doses of Met-Enk injected intracerebrally or subcutaneously, nor the use of various protocols of treatment, did modify the process of tumorigenesis. In contrast, low dose (0.25mg/kg) of Met-Enk injected intracerebrally together with tumor inoculation, significantly reduced tumor growth and prolonged survival rate.