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The combination of cantharidin and anti-angiogenic therapeutics presents synergistic antitumor effects against pancreatic cancer

ABSTRACT: The combination of cantharidin and anti-angiogenic therapeutics presents synergistic antitumor effects against pancreatic cancer

PROVIDER: PRJNA459723 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7119885.fastq.gz	Fastqsanger.gz
	SRR7119886.fastq.gz	Fastqsanger.gz
	SRR7119887.fastq.gz	Fastqsanger.gz
	SRR7119888.fastq.gz	Fastqsanger.gz

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Similar Datasets

The combination of cantharidin and anti-angiogenic therapeutics presents synergistic antitumor effects against pancreatic cancer

Project description:Background: Cantharidin, an active constituent of mylabris, is believed to have anti-tumor activity. Cantharidin selectively inhibit protein phosphatase 2A (PP2A), a repressor of oncogenic kinase pathways (ERK, JNK, NF-κB, and PKC). Cantharidin represses the growth and metastasis of pancreatic cancer cells in vitro. In the present study, we investigated the effects of cantharidin on pancreatic cancer xenografts in vivo. Methods: Cells stably expressing luciferase were used to establish xenograft models. Xenograft growth was evaluated by living imaging. Gene expression was determined using a microarray, real-time PCR, a RayBiotech antibody array, and the Milliplex assay. Results: Surprisingly, cantharidin significantly accelerated xenograft growth. Living imaging showed a rapid distribution of D-luciferin in cantharidin-treated xenografts, suggesting a rich blood supply. Immunohistochemistry confirmed increased angiogenesis. Microarray and antibody array identified upregulated pro-angiogenic and downregulated anti-angiogenic factors. The Milliplex assay suggested elevated secretion of IL-6, IL-8, TNF-α, and VEGF. ERK, JNK, NF-κB, and PKC pathway inhibitors attenuated the cantharidin-induced changes to pro-angiogenic gene expression. PKC pathway-inhibiting tamoxifen or antiangiogenic therapeutics, including Ginsenoside Rg3, bevacizumab, Apatinib, and Endostar antagonized the pro-angiogenic effect of cantharidin or its derivatives. These regimens presented remarkable synergistic antitumor effects in vivo. Conclusion: Although cantharidin presents anti-tumor effects in vitro and has been applied in clinical practice, we revealed an unfavorable pro-angiogenic side effect. We recommend that the clinical application of cantharidin should be performed on the premise of anti-vascularization therapy.

2018-12-06 | GSE114040 | GEO

Extracellular vimentin mimics VEGF and is a target for anti-angiogenic immunotherapy

Project description:Anti-angiogenic anticancer therapies possess immune-stimulatory properties by counteracting pro-angiogenic molecular mechanisms. We report that tumor endothelial cells ubiquitously overexpress and secrete the intermediate filament protein vimentin through type III unconventional mechanisms. Extracellular vimentin is pro-angiogenic and functionally mimics VEGF action, while concomitantly acting as inhibitor of leukocyte-endothelial interactions. Targeting of extracellular vimentin presents a promising anti-angiogenic immunotherapy strategy against cancer. Here we describe profiling of the HUVEC (Human Umbilical Vein Endothelial Cell) proteome, with special emphasis on vimentin (variants) in the different fractions. We have evidence that vimentin is externalized and deposited in the matrix of cultured cells and is as such available for targeted antiangiogenic therapeutics. The aim of the experiment is to determine the protein variants of vimentin in the cell, the secretome, and in the matrix deposited by the cells.

2022-03-29 | PXD024426 | Pride

The combination of cantharidin and antiangiogenic therapeutics presents additive antitumor effects against pancreatic cancer.

Project description:Cantharidin, one of the active components of mylabris, is believed to have antitumor activity. Cantharidin selectively inhibits protein phosphatase 2A (PP2A), which can repress multiple oncogenic kinases (ERK, JNK, PKC, and NF-κB). Researches in vitro have shown that cantharidin suppresses cell viability and metastasis in pancreatic cancer cells. This study aims to investigate the effects of cantharidin on pancreatic cancer xenografts in vivo. Xenograft models were established using cells stably expressing luciferase. Xenograft growth was evaluated by living imaging. Gene expression was determined using a microarray, real-time PCR, a RayBiotech antibody array, and the Milliplex assay. Surprisingly, cantharidin significantly accelerated xenograft growth. Living imaging showed a rapid distribution of D-luciferin in cantharidin-treated xenografts, suggesting a rich blood supply. Immunohistochemistry confirmed increased angiogenesis. Microarray and antibody array identified upregulated proangiogenic and downregulated antiangiogenic factors. The Milliplex assay suggested elevated secretion of IL-6, IL-8, TNF-α, and VEGF. Inhibitors of ERK, JNK, PKC, and NF-κB pathway attenuated the cantharidin-induced changes to proangiogenic gene expression. PKC pathway-inhibiting tamoxifen or antiangiogenic therapeutics, including Ginsenoside Rg3, bevacizumab, Apatinib, and Endostar, antagonized the proangiogenic effect of cantharidin or its derivatives. These regimens presented remarkable additive antitumor effects in vivo. Although cantharidin presents antitumor effects in vitro and has been applied in clinical practice, we revealed an unfavorable proangiogenic side effect. We recommend that the clinical application of cantharidin should be performed on the premise of antivascularization therapy.

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Project description:Systemically administered HMGN1 immunostimulatory peptide with anti-PD-L1 antibody exerts synergistic antitumor effects

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Role of regorafenib in antitumor immunity in hepatocellular carcinoma

Project description:Low-dose regorafenib (5 mg/kg/day, corresponding to about half of human clinical dosage) inhibited tumor growth and angiogenesis in vivo similarly to DC-101 (anti-VEGFR antibody) but produced higher T cell activation and M1 macrophage polarization, Regorafenib increased M1/M2 ratio of BMDMs polarization and proliferation/activation of co-cultured T cells in vitro, indicating angiogenesis-independent immunomodulatory effects. Suppression of p38 kinase phosphorylation and downstream CREB-KLF4 activity in BMDMs by regorafenib reversed M2 polarization. Regorafenib enhanced antitumor efficacy of adoptively transferred antigen-specific T cells, whereas macrophage deletion negated regorafenib’s antitumor effects. Synergistic antitumor efficacy between low-dose regorafenib and anti-PD1 was associated with multiple immune-related pathways in the tumor microenvironment.

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Antitumor immunity induced by antibody-based natural killer cell engager therapeutics armed with not-alpha IL-2 variant

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