Recombinant vascular basement membrane derived multifunctional peptide blocks endothelial cell angiogenesis and neovascularization

Wang, Chengkun; Cao, Ji; Qu, Jiaquan; Li, Yafei; Peng, Bo; Gu, Yue; He, Zhiwei

doi:10.1002/jcb.22735

Cited by 5 publications

(5 citation statements)

References 32 publications

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“…However, the underlying detailed mechanism is not clear. Our previous study confirmed that rVBMDMP also binds integrin αVβ3 (4).…”

Section: Discussionsupporting

confidence: 86%

“…Moreover, rVBMDMP selectively inhibited endothelial cell and human colon cancer cell proliferation, induced endothelial cell apoptosis in vitro and suppressed human colon cancer xenograft growth in Balb/c-nu mice (3). We determined that the interaction of rVBMDMP with αVβ3 integrin is critical for rVBMDMP binding to cells and mediates the rVBMDMP-induced inhibition of proliferation (4).…”

Section: Introductionmentioning

confidence: 99%

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Effects of VBMDMP on the reversal of cisplatin resistance in human lung cancer A549/DDP cells

Wang¹,

Zhang²,

Zhang³

et al. 2014

Oncology Reports

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Abstract.Tumor drug resistance is a major obstacle to cancer chemotherapy. We previously constructed a fusion protein based on two tumstatin-derived sequences named recombinant VBMDM (rVBMDMP). We preliminarily confirmed its inhibition of HUVEC and colon cancer cell growth. The present study further systematically observed the inhibitory effect of rVBMDMP on lung cancer cell growth and analyzed a possible mechanism to provide a theoretical basis for the development of new antitumor protein drugs. The effect of rVBMDMP on human lung adenocarcinoma (A549) and cisplatin-resistant human lung adenocarcinoma (A549/DDP) cell proliferation was evaluated by MTS assay. Hoechst 33342 staining performed together with fluorescence microscopy and immunoblot analysis were used to examine the effects of rVBMDMP on the apoptosis of A549/DDP cells. A protein phosphorylation chip was used to identify changes in rVBMDMP-induced signaling protein phosphorylation. Changes in the phosphatidylinositol 3 kinase (PI3K)/Akt signal transduction pathway and expression of multidrug resistance protein (MRP-2)-related molecules following rVBMDMP treatment in A549/DDP cells were evaluated by western blot analysis. A lung cancer xenograft model was used to evaluate the reversal effect of rVBMDMP on drug-resistance of A549/ DDP cell tumors to cisplatin in vivo. The results demonstrated that rVBMDMP increased the phosphorylation of 79 signaling proteins, including focal adhesion kinase (FAK), caspase-6, Fas, FasL and FAF1 and downregulated 30 signaling proteins, including integrin αV, integrin β3, PI3K/Akt, NF-κB and MRP-2 compared with the controls. rVBMDMP also increased the sensitivity of A549 and A549/DDP cells to cisplatin and directly induced apoptosis, which may be related to MRP-2 and Bcl-2 downregulation. The effects of growth inhibition and apoptosis induction of rVBMDMP on A549/DDP cells may be related to the inhibition of integrin αVβ3 and PI3K/Akt protein phosphorylation. Finally, we observed an increase in cancer cell sensitivity to cisplatin by rVBMDMP using the A549/DDP cell xenograft model in nude mice. Our study suggests that rVBMDMP may be an effective potential chemotherapy sensitizer and may be a viable drug candidate in anticancer therapies.

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“…However, the underlying detailed mechanism is not clear. Our previous study confirmed that rVBMDMP also binds integrin αVβ3 (4).…”

Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Effects of VBMDMP on the reversal of cisplatin resistance in human lung cancer A549/DDP cells

Wang¹,

Zhang²,

Zhang³

et al. 2014

Oncology Reports

View full text Add to dashboard Cite

show abstract

“…Tests were done in triplicate, counting a minimum of 200 total cells each. In addition, apoptotic cells were also analyzed using fluorescence-activated cell sorting (FACS) after staining with annexin V-fluorescein isothiocyanate [23] for determination of phosphatidylserine translocation. Viable cells were negative for both PI and Annexin-V; apoptotic cells were positive for Annexin-V and negative for PI, whereas late apoptotic dead cells displayed both high Annexin-V and PI labeling.…”

Section: Quantitation Of Apoptotic Cellsmentioning

confidence: 99%

Potentiation of arsenic trioxide-induced apoptosis by 8-bromo-7-methoxychrysin in human leukemia cells involves depletion of intracellular reduced glutathione

Xiao

Tang

Yao

et al. 2011

ABBS

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The novel chrysin analog 8-bromo-7-methoxychrysin (BrMC) has been reported to induce apoptosis of various cancer cell lines. Arsenic trioxide (ATO) treatment induces clinical remission in acute promyelocytic leukemia patients. The combination of ATO with other agents has been shown to improve therapeutic effectiveness in vitro and in vivo. In this report, the mechanism of apoptosis induced by treatment with ATO alone or in combination with BrMC was studied in U937, HL-60, and Jurkat cells. Our results demonstrated that BrMC cooperated with ATO to induce apoptosis in human leukemia cells. This co-treatment caused mitochondrial transmembrane potential dissipation and stimulated the mitochondrial apoptotic pathway, as evidenced by cytochrome c release, down-regulation of X-linked inhibitor of apoptosis (XIAP) and Bcl-XL, and up-regulation of Bax. BrMC alone or in combination with ATO, decreased Akt phosphorylation as well as intracellular reduced glutathione (GSH) content. The thiol antioxidant N-acetylcysteine and exogenous GSH restored GSH content and attenuated apoptosis induced by co-treatment with ATO plus BrMC. In contrast, the non-thiol antioxidant butylated hydroxyanisole and mannitol failed to do so. These findings suggest that GSH depletion explains at least in part the potentiation of ATO-induced apoptosis by BrMC.

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“…Once obtained and expanded, immunocytochemical characterization of HUVE‐12 showed positive expression of CD 31 and Flk‐ 1 (current study). This cell line has also been shown by other laboratories to demonstrate angiogenic behaviour such as tube formation (Wang et al ., ). HUVE‐12 cells were split at a density of 1:4. hMSCs (Tulane Center for Gene Therapy; New Orleans, LA, USA) were cultured in αMEM cell culture medium that included Minimum Essential Media (GIBCO®) supplemented with 15% FBS, 1% antibiotic and 2 mM glutamine (GIBCO®).…”

Section: Methodsmentioning

confidence: 97%

Endothelial invasive response in a co-culture model with physically-induced osteodifferentiation

Traphagen

Titushkin

Sun

et al. 2012

J Tissue Eng Regen Med

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Manipulation of stem cells using physicochemical stimuli has emerged as an important tool in regenerative medicine. While 2D substrates with tunable elasticity have been studied for control of stem cell differentiation, we recently developed a stratified co-culture model of angiogenesis of human mesenchymal stem cells (hMSCs) that differentiate on a tunable polydimethylsiloxane (PDMS) substrate, thereby creating a physiologic context for elasticity-induced differentiation. Endothelial cells (EC) were cultured on top of the hMSC construct on a collagen gel to monitor network formation. Media composition influenced EC invasion due to the conditioning media, the reduction of serum and supplemental growth factors, and the addition of recombinant growth factors. Conditioned media, recombinant growth factors and direct co-culture were compared for endothelial cell invasive response using quantitative image analysis. As anticipated, use of recombinant vascular endothelial growth factor (VEGF) induced the deepest EC invasions while direct co-culture caused shallow invasions compared to other conditions. However, endothelial cells displayed lumen-like morphology, suggesting that cell-cell interaction in the co-culture model could mimic sprouting behaviour. In summary, an engineered suitable biochemical and physical environment facilitated endothelial cells to form 3D vessel structures onto hMSCs. These structures were plated on a stiff surface known to induce osteodifferentiation of stem cells. This low cost co-culture system, with its minimal chemical supplementation and physically controllable matrix, could potentially model in vivo potential in engineered and pre-vascularized bone grafts.

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Recombinant vascular basement membrane derived multifunctional peptide blocks endothelial cell angiogenesis and neovascularization

Cited by 5 publications

References 32 publications

Effects of VBMDMP on the reversal of cisplatin resistance in human lung cancer A549/DDP cells

Effects of VBMDMP on the reversal of cisplatin resistance in human lung cancer A549/DDP cells

Potentiation of arsenic trioxide-induced apoptosis by 8-bromo-7-methoxychrysin in human leukemia cells involves depletion of intracellular reduced glutathione

Endothelial invasive response in a co-culture model with physically-induced osteodifferentiation

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