Metastatik Meme Kanseri Hücrelerinde Mtor Üzerine Etkili Bazı Mekanizmaların Araştırılması

Abstract

Signal trunsduction pathways play crucial roles in breast cancer pathogenesis. mTOR, which plays a central role in cell proliferation and interacts with several cell components, is selected as a target in MDA-MB- 231 metastatic, triple negative human breast cancer cell line. The Notch signalling pathway is activated in MDA-MB-231 cell as compared to non metastatic MCF 7 cells. Ion channels are also known to be involved in the emergence of malignant phenotype in cancer cells. For example, the neonatal splice variant of voltage gated sodium channels is activated and contribute to metastatic behaviour of in MDA-MB 231 cells. Thus, we aimed at analysing the effects of Notch-4 receptor and nnav 1.5 sodium channel on mTOR. For this purpose, Phenytoin and gamma secretase inhibitor is used for inhibiting nnav 1.5 sodium channel and Notc-4 respectively. Their effects on mTOR was analysed by detecting the time dendent expression of phosphorylated, active forms of its specific substrates, S6K ve 4E-BP1 by “Western Blot” . Phenytoin, decreased the expression of p-70s6k p-4E-BP1,21% and 23% in 24 hours respectively. While, gamma secretase inhibitor coused a decrease by 66% and 25% in 72 hours. The inhibition of nnav 1.5 activity did not effect cell proliferation significantly. However, inhibition of Notch 4 receptor signalling resulted in 50 % reduction in cell viability in 48 hours. It is concluded that, nNav1.5 and Noç-4 are effective on mTOR activity. Thus, it may be important to consider this central molecule as a system and the co-inhibition of nNav1.5, Notch-4 and probably other cell components may contribute the development of efficient treatment strategies.