Recent studies showed that the activation of prostaglandin (PG) receptor EP1 promotes cell migration and invasion in different cancers. The aim of this study was to investigate the role of EP1 in the proliferation of osteosarcoma (OS) cells in vitro and in vivo. EP1 mRNA and protein levels were analyzed by real-time RT-PCR and Western blot, respectively in human OS cell lines MG63, OS732, U-2OS, HOS and SAOS-2 compared to human fetal osteoblastic hFOB 1.19 cells. MG63 cells were treated with PGE2, EP1 specific agonist 17-PT-PGE2, 17-PT-PGE2 + EP1 specific antagonist SC51089, or DMSO (control). EP1R-siRNA or a non-silencing irrelevant RNA duplex (negative control) were used for the transfection of MG63 cells, followed by PGE2 treatment. Nude mice carrying MG63 xenografts were treated with SC51089 (2 mg/kg/day). MG63 cells/xenografts were analyzed by MTT assay, TUNEL assay, PKC enzyme activity assay, and Western blot (EP1 and apoptotic proteins), and tumor growth/volume was evaluated in mice. EP1 levels were significantly higher in OS cells compared to osteoblasts. PGE2 or 17-PT-PGE2 treatment increased the proliferation and decreased the apoptosis of MG63 cells. Inhibition of EP1 by SC51089 or siRNA markedly decreased the viability of MG63 cells. Similarly, SC51089 treatment significantly inhibited MG63 cell proliferation and promoted apoptosis in vivo. The silencing of EP1 receptor by siRNA or blockade of EP1 signaling by SC51089 activated extrinsic and intrinsic apoptotic pathways both in vivo and in vitro, as evidenced by increased levels of Bax, cyt-c, cleaved caspase-3, caspase-8 and caspase-9. EP1 appears to be involved in PGE2-induced proliferative activity of MG63 cells. Antagonizing EP1 may provide a novel therapeutic approach to the treatment of OS.
Background: Pseudotumours are a rare and serious complication of haemophilia, A slowly growing pseudotumour frequently destroys structures of bone and soft tissues. Surgical resection is the primary method for treatment of proximal pseudotumours. The purpose of this retrospective study was to evaluate the operative methods and clinical results of surgical treatment for those rare cases.Methods: We reviewed nine patients with hemophilic pseudotumours, who received surgical resection treatment in our hospital. The age range was 20-51 years. All operations were performed by one group surgeons. The method of operation depends on the origin and the extent of pseudotumor involvement. With the supplementary of recombinant coagulation factor VIII, six cases received complete resection; one received cytoreduction surgery as the pseudotumor closing to iliac vessel and nerve; two cases received complete resection and construction as bone destruction. Factor substitution was maintained for 14 days. Results: In our series, the average intraoperative blood loss volume was 710±35 ml(range ,240-2100ml). Six patients received blood transfusion during perioperative period. All wounds healed smoothly, no infection or chronic sinus formation. There is no iatrogenic vascular nerve injury in our series. Complete follow-up was performed in all patients. Mean follow-up duration was 14.5months (range, 6–26months). One patient with pseudotumor in the thigh had a recurrence of one year after operation, then secondary operation was performed, Conclusions: Surgical resection for haemophilic pseudotumours is an effctive and safe method . The choice of surgical procedure must be individualized according to the localization and the progress of pseudotumor. However, as relatively few cases and shorter follow-up time in our series. The long-term effects of these patients need further follow-up.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.