Alendronate suppresses tumor angiogenesis by inhibiting Rho activation of endothelial cells☆
Section snippets
Materials and methods
Materials. We used alendronate (sodium hydrate) (TEIJIN LIMITED), which has already been marketed in Japan. Recombinant human VEGF was purchased from Wako (Osaka, Japan). BSA and collagen type I were purchased from Sigma (St. Louis, MO). Rat anti-mouse CD31 monoclonal antibody and growth factor reduced Matrigel were purchased from BD Biosciences (Bedford, MA). The Rho Activation Assay Kit and anti-paxillin monoclonal antibody were obtained from Upstate Biotechnology (Lake Placid, NY). Anti-RhoA
Alendronate inhibits VEGF-induced EC migration
Tumor-associated angiogenesis is known to play an important role in tumor growth and progression in vivo. Previously, we demonstrated that alendronate reduced the tumor burden and inhibited ascites accumulation [3]. In this study, we next examined the direct antiangiogenic effect of alendronate against ECs.
EC migration is an important factor in angiogenesis. We therefore investigated whether alendronate inhibits VEGF-enhanced EC migration. VEGF stimulated the cell migration of HUVECs as
Discussion
Clinical observations have confirmed that VEGF status is associated with the extent of neovascularization [12] and prognosis in many solid tumors [13]. There are some discrepancies among the previously reported effects of NBPs on tumor-derived VEGF expression. It was reported that non-cytotoxic concentrations of minodronate did not affect the production of VEGF by renal cell cancer [14]. On the other hand, NBPs were reported to reduce circulating VEGF in cancer patients [15]. Therefore, we
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Alendronate/dexamethasone combination therapy worsens soft and hard tissue wound healing around implants in rat maxillae
2021, BoneCitation Excerpt :Analyzed sites (connective tissue of the tooth extraction sockets in the previous study [34] versus periapical lesions [49] versus around implants in the present study), experimental animals, and drug metabolism differences in animal species (mice in the previous study [48] versus rats in the present study), and administration duration and dose (1 week in the previous study [49] versus 14 weeks in the present study) may lead to the different effects of ALN administration on blood formation. However, it has been reported that ALN suppressed prostate cancer growth by inhibiting angiogenesis when PC-3 cells were implanted into nude mice [50] and tumor angiogenesis via inhibition of Rho activation in an in vitro study [51]. Their results were partially in accordance with the present data, although the common experimental situations of the previous studies were associated with tumor angiogenesis [50,51].
Nano-technology based carriers for nitrogen-containing bisphosphonates delivery as sensitisers of γδ T cells for anticancer immunotherapy
2017, Advanced Drug Delivery ReviewsCorrelation of changes in the mandible and retina/choroid vasculature of a rat model of BRONJ
2015, Journal of Cranio-Maxillofacial SurgeryCitation Excerpt :Other studies have suggested that bisphosphonates disrupt normal lipid modification of Rho, Ras and Rac within endothelial cells (Hashimoto et al., 2007). These results suggest that inhibition of endothelial cell activities may play a major role in the antiangiogenic activities that are seen with high dose bisphosphonate treatment but are not necessarily part of the mechanism found in the osteonecrosis that results from other medications (Hashimoto et al., 2007; Hasmim et al., 2007; Bezzi et al., 2003). In the present study, after 4 weeks, the mRNA for VEGF-A, but not VEGFR-2, was increased in Control rats vs. ZA-treated animals.
Stimulation of in-vitro angiogenesis by low concentrations of risedronate is mitigated by 1,25-dihydroxyvitamin D<inf>3</inf> or 24,25-dihydroxyvitamin D<inf>3</inf>
2015, Journal of Steroid Biochemistry and Molecular BiologyCitation Excerpt :Nevertheless, there is very little information about the angiogenic activity of others N-BP, such as risedronate, and even less data for low doses. Yet a general antiangiogenic effect of the N-BP family, including risedronate, has been proposed [5–9]. Thus, one of the pivotal reports [10] showed that zoledronate exhibits a dose-response inhibition of the endothelial-cell proliferation and the microcapillary-like tube formation activities, being 10−6 and 10−4 M the lower and higher concentrations used, respectively.
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This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan.