Inhibition of transforming growth factor beta/SMAD signal by MiR-155 is involved in arsenic trioxide-induced anti-angiogenesis in prostate cancer.
Bottom Line: Furthermore, As2 O3 improved the expression of miR-155 via DNA-demethylation.MiR-155, which targeted the SMAD2-3'UTR, decreased the expression and function of SMAD2.Knockdown of miR-155 abolished the As2 O3 -induced inhibitions of the TGF-β/SMAD2 signaling, the vascular endothelial growth factor secretion and angiogenesis.
Affiliation: Affiliated Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing, China.Show MeSH
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Mentions: First, we determined the effects of As2O3 on the viabilities of human prostate carcinoma PC-3 and LNCaP cells. As shown in Figure 1(a), there were decreases of viabilities in cells exposed to 4 μM As2O3; however, no detectable attenuations of viabilities were observed in cells exposed to 0.5, 1 and 2 μM As2O3. Next, we used ELISA to investigate the effects of As2O3 on the VEGF secretion in these cells. As shown in Figure 1(b), As2O3 inhibited the secretions of VEGF in a dose-dependent manner. Finally, we used the tube formation assay to further detect the functions of As2O3 in the angiogenic ability of prostate carcinoma cells. To avoid the addition of As2O3 to the endothelial cells in the tube formation assay, we pre-treated PC-3 and/or LNCaP cells with 0 or 2 μM As2O3 for 48 h, followed by a conventional culture in fresh medium for another 24 h. The conditioned mediums were then collected. We treated human umbilical vein endothelial cells (HUVEC) with these conditioned mediums, respectively. Our data showed that there was decreased cell viability (Fig. S1a) and attenuated formations of tubes in HUVEC (Fig. 1c,d) incubated with the conditioned mediums collected from As2O3-pre-treated cells. Importantly, there was no detectable inhibition of tube formation after HUVEC were directly exposed to As2O3 (Fig. S1b). These results suggest that As2O3 attenuates the angiogenic abilities of prostate carcinoma cells, in which the inhibitions of VEGF secretion are involved.
Affiliation: Affiliated Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing, China.