RESUMO
Cancer-derived mesenchymal stem cells (MSCs) seem to play an important role in mediating tumor angiogenesis. Recently, curcumin has been shown to display multiple therapeutic properties, including anticancer activity. In the present study, we have tried to explore the role of curcumin in regulating gastric cancer cells-derived mesenchymal stem cells (GC-MSCs) mediated angiogenesis. Our results showed that curcumin attenuated the high expression levels of fibroblast proteins (α-SMA & Vimentin) in GC-MSCs. Its treatment also inhibited GC-MSCs induced human umbilical vein endothelial cells (HUVEC) tube formation, migration and colony formation. Furthermore, it was noticed that curcumin abrogated NF-κB signaling activity and VEGF production in GC-MSCs. Next, to establish the link between regulation of NF-κB/VEGF signaling by curcumin, and its influence on GC-MSC-derived angiogenesis, we pretreated GC-MSCs with either NF-κB inhibitor PDTC or a neutralizing antibody against VEGF (NA-VEGF), and then collected conditioned media (CM). The HUVEC cells were then cultured in this conditioned media to test their ability to form tubes, migrate and form colonies. Our results demonstrated that NF-κB/VEGF signaling is important for GC-MSCs induced tube formation, migration and colony formation in HUVEC cells. Moreover, we also observed that NF-κB/VEGF signaling regulated VEGF expression of gastric cancer cells both in vitro and in vivo. Overall, our study indicated that curcumin may serve as a novel therapeutic target for GC-MSCs derived angiogenesis, by inhibiting NF-κB/VEGF signaling.
RESUMO
MicroRNA-21 was upexpressed in gastric cancer (GC) indicating that it is a potential diagnostic biomarker for GC. In this study, 50 GC patients and 50 healthy controls were recruited. miR-21 levels in serum and peripheral blood mononuclear cells (PBMCs) were quantified using quantitative real-time PCR. CA199, and CEA were measured using electrochemiluminescence assay. The sensitivity and specificity of circulating miR-21, CA199 and CEA in GC diagnosis, the correlation of circulating miR-21 to clinicopathological features, and the diagnostic value of miR-21 in different GC stages were determined. The levels of miR-21 in both serum and PBMCs increased significantly in GC patients comparing to healthy controls; however, no correlation was observed between circulating miR-21 level and clinicopathological features. The sensitivity and specificity of miR-21 in serum and PBMCs, and CA199 and CEA in GC diagnosis were 88.4%, 79.6%, 81.3%, 73.4%, 60.5%, 55.9%, and 68.6%, 59.3%, respectively. The positive prediction rates of circulating miR-21 in GC stages I to IV were all around 90%, while those of CA199 and CEA were around or less than 50%. Our data suggest circulating miR-21 (both in serum and in PBMCs) can serve as a good biomarker for GC and could be used in diagnosis of early (stage I) and late GC (stage IV).
Assuntos
Biomarcadores Tumorais/sangue , MicroRNAs/sangue , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Adulto , Idoso , Antígenos Glicosídicos Associados a Tumores/metabolismo , Antígeno Carcinoembrionário/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/sangueRESUMO
MicroRNAs might act as oncogenes or tumor suppressors in cancer. Recent studies have shown that miR-421 is up-regulated in human gastric cancer. Here, we found that miR-421 was over-expressed in gastric cancer tissues and cell lines. Bioinformatics analysis predicted that the caspase-3 gene was a target of miR-421. Caspase-3 was negatively regulated by miR-421 at the post-transcriptional level. Bax and Bcl-2 were also regulated by miR-421. Moreover, tumor necrosis factor receptor-I and -II, death receptors in the apoptosis pathway, were up-regulated by miR-421. The over-expression of miR-421 promoted gastric cancer cell growth and inhibited apoptosis of the BGC-823 gastric cancer cell line. These observations indicate that miR-421 acts as a tumor promoter by targeting the caspase-3 gene and preventing apoptosis of gastric cancer cells through inhibition of caspase-3 expression. These findings contribute to our understanding of the functions of miR-421 in gastric cancer.