The effect of aflibercept and arsenic trioxide on the proliferation, migration and apoptosis of oral squamous cell carcinoma in vitro.

Aflibercept and arsenic trioxide drugs apply a cytotoxic effect on some human cancer cell lines. However, no more study has followed the effects of both drugs, especially arsenic trioxide, on oral squamous cell carcinoma (OCC). We used three OCC lines as a model to show the effect of these drugs on the genetically complex disease and investigate its targeted therapy. In this study, three human OCC cell lines were used from different patients. We treated cell lines with both medications to detect the effect and relevant molecular basis. First, methyl thiazolyl tetrazolium (MTT) assay was performed to detect the cytotoxicity effect and cell growth. Second, flow cytometry, gene and protein expression were performed to evaluate the anti-angiogenic effect on OCC lines. Next apoptosis was analyzed by flow cytometry. Finally, clonogenesis capacity and cell migration were assessed by colony formation assay and wound healing, respectively. Aflibercept had no cytotoxic effect on the three OCC cell lines but decreased cell growth rate. Arsenic trioxide had a significant cytotoxic effect on three cell lines. Our results demonstrated that both drugs significantly decreased endoglin, VEGFA, and VEGFB expression. In addition, Migration and colony formation assays confirmed that these drugs have significant anti-proliferative and anti-migration effect on oral carcinoma cells. These results revealed that both medications might be a potential drug for the management of oral cancer patients.

Decoy-DNA against special AT-rich sequence binding protein 1 inhibits the growth and invasive ability of human breast cancer.

"Triple-negative" (TN) breast cancers, which are characterized by estrogen receptor (-), progesterone receptor (-), and human epidermal growth factor receptor 2 (-), are typically associated with poor prognosis because of their aggressive tumor phenotypes. In recent years, the number of patients with breast cancers has remarkably increased, but there are only few available drugs for treatment of TN breast cancers. The development of novel drugs targeting TN breast cancer is urgently required. In the present study, we focused on the function of special AT-rich sequence binding protein 1 (SATB1) as a target molecule for the treatment of TN breast cancers. By recruiting chromatin remodeling enzymes and transcriptional factors, SATB1 regulates the expression of >1,000 genes related to cell growth and translocation. We synthesized a decoy DNA against SATB1, including the recognition sequence of SATB1. We examined the inhibitory effects of the decoy DNAs on cellular proliferation of a TN metastatic breast cancer cell line (MDA-MB-231). SATB1-decoy DNA inhibited the proliferation of MDA-MB-231 cells. Especially, it was significant that SATB1-decoy DNA drastically reduced the invasive and metastatic capacity of MBA-MB-231 cells. Further, in the case of MCF7 cells (SATB1-negative breast cancer cell line), SATB1-decoy DNA did not exhibit any inhibitory effect. These data suggest that SATB1-decoy DNA may be an effective candidate for use as a molecular-targeting drug for treatment of TN breast cancer.

Role of growth factors in improved skin flap viability caused by phosphodiesterase-5 inhibitor.

Flap necrosis is one of the major complications of reconstructive surgery and sildenafil citrate has been shown to decrease flap necrosis in preclinical animal models. However, the mechanisms underlying sildenafil's therapeutic efficacy are not known. As with other phosphodiesterase 5 selective inhibitors, sildenafil causes vasodilation and enhanced blood flow. In addition, sildenafil can also alter gene expression. This study is designed to test the hypothesis that increased expression of angiogenic growth factors may be responsible for therapeutic efficacy of sildenafil. A modified McFarlane flap measuring 3 x 10 cm was created on the dorsal skin of male Sprague-Dawley rats. For growth factor expression experiment, rats were administered either vehicle or sildenafil 10 mg/Kg intraperitoneal (IP). Ribonucleic acid (RNA) extracted from skin flap was analyzed to assess the messenger ribonucleic acid (mRNA) levels of different angiogenic growth factors. For skin flap viability experiment, fibrin film impregnated with vehicle, fibroblast growth factor (FGF) (5.0 microg) or vascular endothelial growth factor (VEGF) (2.0 microg) was applied to the wound. The skin flap was then returned to its native position and stapled in place. Total affected area (area of necrosis and blood flow stasis) of each rat on postoperative day 14 was analyzed with orthogonal polarization spectral imaging. Daily systemic treatment with sildenafil significantly (P < 0.05) increased the expression of FGF1 and FGF Receptor 3 on postoperative day 3 by 5.08- and 4.78-fold, respectively. In addition, sildenafil increased the expression of VEGF-A, VEGF-B, and VEGF-C by 2.66-, 2.02-, and 2.00-fold, respectively. Subcutaneous treatment with FGF but not VEGF-A tended to decrease total affected area in rats. These data demonstrate that sildenafil altered the expression of FGF and VEGF. Altered expression of growth factors may be, at least partly, responsible for the beneficial effects of sildenafil citrate on skin viability.

Prophylactic but not therapeutic activity of a monoclonal antibody that neutralizes the binding of VEGF-B to VEGFR-1 in a murine collagen-induced arthritis model.

OBJECTIVE: To assess the therapeutic potential of a mAb that neutralizes the binding of VEGF-B to VEGFR-1, to inhibit the pathogenesis of CIA in mice. METHODS: CIA was induced in C57BL6/J and DBA-1 mice by intradermal injection of chick collagen type II (CII) in adjuvant. A neutralizing VEGF-B mAb or an isotype control mAb was then administered by intraperitoneal injection twice weekly beginning either post CII booster injection but prior to or immediately following clinical disease diagnosis. RESULTS: Neutralizing VEGF-B mAb inhibited the development of CIA in C57BL6/J mice in a dose-dependent manner when administered following the CII booster injection, but prior to clinical disease diagnosis. This result was also confirmed in DBA-1 strain mice. In contrast, the neutralizing VEGF-B mAb had no measurable effect on disease severity or progression when treatment commenced from the day of clinical disease diagnosis. CONCLUSIONS: Treatment with an mAb that neutralizes the binding of VEGF-B to VEGFR-1 exhibits prophylactic but not therapeutic actions in a mouse model of RA. These data indicate that while VEGF-B/VEGFR-1 signalling is involved in the early development of arthritis it may not be required for maintenance or progression of established disease.