Activation of the cell membrane angiotensin AT2 receptors in human leiomyosarcoma cells induces differentiation and apoptosis by a PPARγ - dependent mechanism.

摘要: Angiotensin II (Ang II), the main effector peptide of renin-angiotensin system (RAS), acting on AT1 and AT2 receptors participates in regulation proliferation, differentiation apoptosis tumour cells. The peroxisome-proliferator activated receptor γ (PPARγ) its ligands exert anti-tumour effects various human cancer cell lines. present study investigates initiated by AT1- stimulation SK-UT-1 cells, a leiomyosarcoma line, clarifies role PPARγ receptor-induced apoptosis.Selective was achieved incubation cells with Ang (10-6 M) presence selective antagonist, PD 123177 losartan (10-5 M), respectively, GW 9662, used at concentration 10-6 M. expression smooth muscle markers, SM22α calponin, analysed RNA- protein levels using RT PCR Western blot, which also to quantify Bcl-2-, Bax- cleaved caspase-3 proteins. translocation AT2-receptor interacting 1 (ATIP1) nuclei studied blot immunofluorescence staining. mitochondrial status metabolic activity response activation were assessed quantification 99mTc - sestamibi 2´-deoxy-2´-[18F]fluoro-D-glucose uptake.AT1 did not any profound quiescent induced time-dependent. A short, 3 6 h lasting promotes differentiation, i.e increases mRNA- whereas sustained for 48 activates intrinsic apoptotic pathway, as evidenced reduced numbers, down-regulation anti-apoptotic Bcl-2 increased Bax caspase-3. reversed clearly implying PPARγ-dependent mechanism. Our results demonstrate co-localisation protein, ATIP1, an accumulation ATIP1 nuclear fraction stimulation. via favours important functional this quiescent, slow-cycling provides rationale use antagonists treatment leiomyosarcomas.