Influence of Interferon-Alpha Combined with Chemo (Radio) Therapy on Immunological Parameters in  Pancreatic Adenocarcinoma

Karakhanova, Svetlana; Mosl, Beate; Harig, Sabine; Ahn, Katharina von; Fritz, Jasmin; Schmidt, Jan; Jäger, Dirk; Werner, Jens; Bazhin, Alexandr V.

doi:10.3390/ijms15034104

Cited by 14 publications

(23 citation statements)

References 36 publications

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“…Earlier, we have showed that in human PDAC cells, the phosphorylation of CREB, ERK1/2, GSK−3, JNK1, JNK2/3, and P38 can be affected by DT3 (Karakhanova et al 2014b). Now, we have analyzed the impact of DT3 on in vivo phosphorylation of these signaling proteins in tumors of PDAC-bearing mice after their treatment with DT3 (Fig.…”

Section: Dt3 Decreases Phosphorylation Of Gsk−3 P38 and Creb In Murmentioning

confidence: 97%

“…Cell viability after DT3 treatment was analyzed both with a EZ4U Kit (Biomedica, Austria) and with a ApoTox-Glo™ Triplex Assay Kit (Promega, USA), and proliferation was assessed with a BrdU Cell Proliferation Assay Kit (Millipore, USA), as previously described (Karakhanova et al 2014b). At least three independent experiments were performed for each assay.…”

Section: Cell Viability and Proliferation Assaysmentioning

confidence: 99%

“…Migration and invasion assays were performed with a CytoSelect™ Cell Migration and Invasion Assay Kit (Cell Biolabs, Inc., USA), as described previously (Karakhanova et al 2014b) for three independent experiments.…”

Section: Migration and Invasion Assaysmentioning

confidence: 99%

“…Apoptosis after DT3 treatment was measured using the ApoTox-Glo™ Triplex Assay Kit (Promega, USA) and the Annexin V and ethidium homodimer III staining with the Apoptotic/Necrotic Cells Detection Kit (PromoKine, Germany) as described previously (Karakhanova et al 2014b). Ten micromolar staurosporine or 100 μM ionomycin were used as a positive control for apoptosis or necrosis, respectively.…”

Section: Apoptosis and Necrosis Assaysmentioning

confidence: 99%

“…Western blot analysis was performed as described elsewhere (Karakhanova et al 2014b). Briefly, 10 μg of total protein per lane were separated in a 12.5 % polyacrylamide gel.…”

Section: Western Blot Analysismentioning

confidence: 99%

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Anti-tumor properties of the cGMP/protein kinase G inhibitor DT3 in pancreatic adenocarcinoma

Soltek

Karakhanova

Golovastova

et al. 2015

Naunyn-Schmiedeberg's Arch Pharmacol

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Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers in the world. Therefore, new therapeutic options are urgently needed to improve the survival of PDAC patients. Protein kinase G (PKG) conducts the interlude of cGMP signaling which is important for healthy as well as for cancer cells. DT3 is a specific inhibitor of PKG, and it has been shown to possess an anti-tumor cytotoxic activity in vitro. The main aim of this work was to investigate anti-tumor effects of DT3 upon PDAC in vivo.Expression of PKG was assessed with real-time PCR analysis in the normal and tumor pancreatic cells. In vitro cell viability, proliferation, apoptosis, necrosis, migration, and invasion of the murine PDAC cell line Panc02 were assessed after DT3 treatment. In vivo anti-tumor effects of DT3 were investigated in the murine Panc02 orthotopic model of PDAC. Western blot analysis was used to determine the phosphorylation state of the proteins of interest.Functional PKGI is preferentially expressed in PDAC cells. DT3 was capable to reduce viability, proliferation, and migration of murine PDAC cells in vitro. At the same time, DT3 treatment did not change the viability of normal epithelial cells of murine liver. In vivo, DT3 treatment reduced the tumor volume and metastases in PDAC-bearing mice, but it was ineffective to prolong the survival of the tumor-bearing animals. In addition, DT3 treatment decreased phosphorylation of GSK-3, P38, and CREB in murine PDAC.Inhibition of PKG could be a potential therapeutic strategy for PDAC treatment which should be carefully validated in future pre-clinical studies.

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Section: Dt3 Decreases Phosphorylation Of Gsk−3 P38 and Creb In Murmentioning

confidence: 97%

Section: Cell Viability and Proliferation Assaysmentioning

confidence: 99%

Section: Migration and Invasion Assaysmentioning

confidence: 99%

Section: Apoptosis and Necrosis Assaysmentioning

confidence: 99%

“…Western blot analysis was performed as described elsewhere (Karakhanova et al 2014b). Briefly, 10 μg of total protein per lane were separated in a 12.5 % polyacrylamide gel.…”

Section: Western Blot Analysismentioning

confidence: 99%

See 3 more Smart Citations