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Cited by 37

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Targeting the Janus-activated kinase-2-STAT3 signalling pathway in pancreatic cancer using the HSP90 inhibitor ganetespib

Nagaraju, Ganji Purnachandra, Mezina, Anya, Shaib, Walid L., Landry, Jerome, El-Rayes, Bassel F.·2016·European Journal of Cancer
DOI 10.1016/j.ejca.2015.10.057
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Abstract

Background Pancreatic cancer (PC) is an aggressive malignancy characterised by chemoresistance. HSP90 is important for stabilisation of proteins, cell signalling and malignant growth. We hypothesised that ganetespib, an HSP90 inhibitor, can inhibit PC cell growth by interfering with multiple signalling cascades, including the Janus-activated kinase (JAK)-STAT pathway, and act synergistically with chemotherapeutic drugs. Methods The effects of ganetespib were evaluated in ASPC-1, HPAC, MIA PaCA-2 and PANC-1 cell lines using a cell proliferation assay. Effects on the expression of phosphoinositide 3-kinase (PI3K)/AKT, mitogen-activated protein kinase (MAPK) and JAK-STAT pathways were examined by Western blot. JAK2 and STAT3 were knocked down by transient transfection with JAK2 or STAT3 small interfering RNA. ASPC-1 and HPAC cell lines were tested for sensitivity to ganetespib, 5-fluorouracil/oxaliplatin, and gemcitabine/paclitaxel, alone and in combination, using an in vivo tumour xenograft model. Results Ganetespib significantly decreased cell proliferation in all tested PC cell lines. Ganetespib decreased the activation of extracellular signal-related kinase (ERK), PI3K/AKT, and c-Jun NH2-terminal kinase (JNK) signalling molecules and diminished the activation of STAT3 in an additive manner with isolated downregulation of JAK2 expression. In animal models, ganetespib potentiated the effects of 5-fluouracil/oxaliplatin and gemcitabine/paclitaxel, as measured by tumour volume.…

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Metadata

Authors
Nagaraju, G. P., Mezina, A., Shaib, W. L., Landry, J., & El-Rayes, B. F.
ORCID
Nagaraju, Ganji Purnachandra
Venue
European Journal of Cancer
Publisher
Elsevier BV
Published
2016-01
Volume
52
Pages
109-119
ISSN
0959-8049
DOI
10.1016/j.ejca.2015.10.057
Cited by
37
References
3
Language
en
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)

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CoChat. (2026). Citation check: Targeting the Janus-activated kinase-2-STAT3 signalling pathway in pancreatic cancer using the HSP90 inhibitor ganetespib. https://app.cochat.ai/papers/10.1016/j.ejca.2015.10.057
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Nagaraju, G. P., Mezina, A., Shaib, W. L., Landry, J., & El-Rayes, B. F. (2016). Targeting the Janus-activated kinase-2-STAT3 signalling pathway in pancreatic cancer using the HSP90 inhibitor ganetespib. European Journal of Cancer. https://doi.org/10.1016/j.ejca.2015.10.057

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