Financiado en parte por Bayer Corporation
Synergistic activity of sorafenib and sulforaphane abolishes pancreatic cancer stem cell characteristics
Rausch V, Liu L, Kallifatidis G, Baumann B, Mattern J, Gladkich J, Wirth T, Schemmer P, Büchler MW, Zöller M, Salnikov AV, Herr I
Cancer research · 147 citas
Etiquetas de revisión
Financiado por la industriaDatos neutrales que nuestra revisión registró sobre cómo se hizo este estudio. Describen el método, nunca si nos gusta el resultado.
Cómo se estudió
- Diseño
- Estudio in vitro o de mecanismos (clasificado por nuestro filtro de IA)
- Estudiado en
- Personas, más trabajo en animales o laboratorio
- Resultado principal
- Eventos clínicos como enfermedad o muerte
Quién lo pagó
- Financiación
- Financiado por la industria
- Empresa
- Bayer Corporation
- Gobierno
- China Scholarship Council
Según 2 financiadores declarados.
Publicación
- Publicado
- 2010-06-08 · Cancer Res · vol. 70 · número 12 · págs. 5004–5013
- Editorial
- American Association for Cancer Research
- Citado
- 210 citas · más que el 99% de estudios similares · 9.2× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 38 trabajos
- Acceso
- De pago
- Áreas de investigación
- Genomics, phytochemicals, and oxidative stress · PI3K/AKT/mTOR signaling in cancer · Quinazolinone synthesis and applications
- Palabras clave
- Sulforaphane, Pancreatic cancer, Downregulation and upregulation, Cancer research, Sorafenib, Angiogenesis, Apoptosis, Cancer stem cell, Epithelial–mesenchymal transition, Cell growth, Cancer, Metastasis, Cancer cell, Stem cell, Chemistry, Biology, Medicine, Cell biology, Internal medicine, Biochemistry, Hepatocellular carcinoma
- MeSH
- cells, cultured, spheroids, cellular, fibroblasts, skin, animals, humans, mice, mice, nude, pancreatic neoplasms, neovascularization, pathologic, thiocyanates, benzenesulfonates, isothiocyanates, sulfoxides, phenylurea compounds, niacinamide, pyridines, isoenzymes, aldehyde dehydrogenase, luciferases, nf-kappa b, rna, messenger, antineoplastic combined chemotherapy protocols, immunoblotting, blotting, western, immunoenzyme techniques, electrophoretic mobility shift assay, colony-forming units assay, xenograft model antitumor assays, reverse transcriptase polymerase chain reaction, apoptosis, cell proliferation, drug synergism, female, retinal dehydrogenase, neoplastic stem cells, sorafenib, aldehyde dehydrogenase 1 family
12 autores
- Vanessa Rausch🇩🇪German Cancer Research Center; Universität Ulm; Heidelberg University
- Li Liu🇩🇪German Cancer Research Center; Universität Ulm; Heidelberg University
- Georgios Kallifatidis🇩🇪German Cancer Research Center; Universität Ulm; Heidelberg University
- Bernd Baumann🇩🇪German Cancer Research Center; Universität Ulm; Heidelberg University
- Jürgen Mattern🇩🇪German Cancer Research Center; Universität Ulm; Heidelberg University
- Jury Gladkich🇩🇪German Cancer Research Center; Universität Ulm; Heidelberg University
- Thomas Christian Wirth🇩🇪German Cancer Research Center; Universität Ulm; Heidelberg University
- Peter Schemmer🇩🇪German Cancer Research Center; Universität Ulm; Heidelberg University
- Markus W. Büchler🇩🇪German Cancer Research Center; Universität Ulm; Heidelberg University
- Margot Zöller🇩🇪German Cancer Research Center; Universität Ulm; Heidelberg University
- Alexei V. Salnikov🇩🇪German Cancer Research Center; Universität Ulm; Heidelberg University
- Ingrid Herr🇩🇪German Cancer Research Center; Universität Ulm; Heidelberg University
Resumen
El texto original del estudio, en el idioma en que se publicó.
Recent evidence suggests that pancreatic cancer and other solid tumors contain a subset of tumorigenic cells capable of extensive self-renewal that contribute to metastasis and treatment resistance. Sorafenib (SO) is a promising new multikinase inhibitor for treatment of advanced kidney and liver cancers. We report here targeting of pancreatic cancer stem cells (CSC) by SO and the development of a strategy to enhance this effect. Although SO administration diminished clonogenicity, spheroid formation, aldehyde dehydrogenase 1 (ALDH1) activity, growth on immunodeficient mice, proliferation, and angiogenesis and induced apoptosis, we observed SO-induced activation of NF-kappaB associated with survival and regrowth of spheroids. For enhanced elimination of CSC characteristics by SO, we cotreated cells with sulforaphane (SF). This broccoli isothiocyanate was recently described to eliminate pancreatic CSCs by downregulation of NF-kappaB activity without inducing toxic side effects. On combination treatment, SF completely eradicated SO-induced NF-kappaB binding, which was associated with abrogated clonogenicity, spheroid formation, ALDH1 activity, migratory capacity, and induction of apoptosis. In vivo, combination therapy reduced the tumor size in a synergistic manner. This was due to induction of apoptosis, inhibition of proliferation and angiogenesis, and downregulation of SO-induced expression of proteins involved in epithelial-mesenchymal transition. Our data suggest that SF may be suited to increase targeting of CSCs by SO.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial.
Confianza de la comunidad
Cargando…
¿Cuánto confías en los hallazgos de este estudio?
Comentarios
¿Algo está mal aquí?
Señala este estudio si su información, etiquetas o financiación parecen incorrectas. Un editor revisa cada señalamiento.
Información educativa sobre investigación publicada. No es consejo médico ni una recomendación para empezar o dejar nada.