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HSP90 is a promising target in gemcitabine and 5-fluorouracil resistant pancreatic cancer

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HSP90 is a promising target in gemcitabine and 5-fluorouracil resistant pancreatic cancer. / Ghadban, Tarik; Dibbern, Judith L; Reeh, Matthias; Miro, Jameel T; Tsui, Tung Y; Wellner, Ulrich; Izbicki, Jakob R; Güngör, Cenap; Vashist, Yogesh K.

In: APOPTOSIS, Vol. 22, No. 3, 03.2017, p. 369-380.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Ghadban, T, Dibbern, JL, Reeh, M, Miro, JT, Tsui, TY, Wellner, U, Izbicki, JR, Güngör, C & Vashist, YK 2017, 'HSP90 is a promising target in gemcitabine and 5-fluorouracil resistant pancreatic cancer', APOPTOSIS, vol. 22, no. 3, pp. 369-380. https://doi.org/10.1007/s10495-016-1332-4

APA

Ghadban, T., Dibbern, J. L., Reeh, M., Miro, J. T., Tsui, T. Y., Wellner, U., Izbicki, J. R., Güngör, C., & Vashist, Y. K. (2017). HSP90 is a promising target in gemcitabine and 5-fluorouracil resistant pancreatic cancer. APOPTOSIS, 22(3), 369-380. https://doi.org/10.1007/s10495-016-1332-4

Vancouver

Ghadban T, Dibbern JL, Reeh M, Miro JT, Tsui TY, Wellner U et al. HSP90 is a promising target in gemcitabine and 5-fluorouracil resistant pancreatic cancer. APOPTOSIS. 2017 Mar;22(3):369-380. https://doi.org/10.1007/s10495-016-1332-4

Bibtex

@article{2566c1a72a8a46bba050e4188d467c29,
title = "HSP90 is a promising target in gemcitabine and 5-fluorouracil resistant pancreatic cancer",
abstract = "Chemotherapy (CT) options in pancreatic cancer (PC) are limited to gemcitabine and 5-fluorouracil (5-FU). Several identified molecular targets in PC represent client proteins of HSP90. HSP90 is a promising target since it interferes with many oncogenic signaling pathways simultaneously. The aim of this study was to evaluate the efficacy of different HSP90 inhibitors in gemcitabine and 5-FU resistant PC. PC cell lines 5061, 5072 and 5156 were isolated and brought in to culture from patients being operated at our institution. L3.6pl cell line served as a control. Anti-proliferative efficacy of three different HSP90 inhibitors (17-AAG, 17-DMAG and 17-AEPGA) was evaluated by the MTT assay. Alterations in signaling pathway effectors and apoptosis upon HSP90 inhibition were determined by western blot analysis and annexin V/PI staining. The cell lines 5061, 5072 and 5156 were resistant to gemcitabine and 5-FU. In contrast 17-AAG and the water-soluble derivates 17-DMAG and 17-AEPGA displayed high anti-proliferative activity in all tested cell lines. The calculated IC50 was below 1 µM. Highly significant down regulation of epidermal-growth-factor-receptor, insulin-like-growth-factor-receptor-1, AKT and MAPK reflected the intracellular molecular signaling-network disruption. Furthermore, besides HSP70 also HSP27 was upregulated in all cell lines. Apoptosis occurred early under HSP90 inhibition and was determined by annexin V/PI staining and CASPASE-3 and PARP assay. In contrast, gemcitabine treated cells did not show any apoptosis. HSP90 inhibition disrupts multiple signaling cascades in gemcitabine and 5-FU resistant PC simultaneously and promotes cancer cell apoptosis. Watersoluble 17-DMAG is equally effective as 17-AAG. HSP27, besides HSP70, may represent an effective response marker of successful HSP90 inhibition.",
author = "Tarik Ghadban and Dibbern, {Judith L} and Matthias Reeh and Miro, {Jameel T} and Tsui, {Tung Y} and Ulrich Wellner and Izbicki, {Jakob R} and Cenap G{\"u}ng{\"o}r and Vashist, {Yogesh K}",
year = "2017",
month = mar,
doi = "10.1007/s10495-016-1332-4",
language = "English",
volume = "22",
pages = "369--380",
journal = "APOPTOSIS",
issn = "1360-8185",
publisher = "Springer Netherlands",
number = "3",

}

RIS

TY - JOUR

T1 - HSP90 is a promising target in gemcitabine and 5-fluorouracil resistant pancreatic cancer

AU - Ghadban, Tarik

AU - Dibbern, Judith L

AU - Reeh, Matthias

AU - Miro, Jameel T

AU - Tsui, Tung Y

AU - Wellner, Ulrich

AU - Izbicki, Jakob R

AU - Güngör, Cenap

AU - Vashist, Yogesh K

PY - 2017/3

Y1 - 2017/3

N2 - Chemotherapy (CT) options in pancreatic cancer (PC) are limited to gemcitabine and 5-fluorouracil (5-FU). Several identified molecular targets in PC represent client proteins of HSP90. HSP90 is a promising target since it interferes with many oncogenic signaling pathways simultaneously. The aim of this study was to evaluate the efficacy of different HSP90 inhibitors in gemcitabine and 5-FU resistant PC. PC cell lines 5061, 5072 and 5156 were isolated and brought in to culture from patients being operated at our institution. L3.6pl cell line served as a control. Anti-proliferative efficacy of three different HSP90 inhibitors (17-AAG, 17-DMAG and 17-AEPGA) was evaluated by the MTT assay. Alterations in signaling pathway effectors and apoptosis upon HSP90 inhibition were determined by western blot analysis and annexin V/PI staining. The cell lines 5061, 5072 and 5156 were resistant to gemcitabine and 5-FU. In contrast 17-AAG and the water-soluble derivates 17-DMAG and 17-AEPGA displayed high anti-proliferative activity in all tested cell lines. The calculated IC50 was below 1 µM. Highly significant down regulation of epidermal-growth-factor-receptor, insulin-like-growth-factor-receptor-1, AKT and MAPK reflected the intracellular molecular signaling-network disruption. Furthermore, besides HSP70 also HSP27 was upregulated in all cell lines. Apoptosis occurred early under HSP90 inhibition and was determined by annexin V/PI staining and CASPASE-3 and PARP assay. In contrast, gemcitabine treated cells did not show any apoptosis. HSP90 inhibition disrupts multiple signaling cascades in gemcitabine and 5-FU resistant PC simultaneously and promotes cancer cell apoptosis. Watersoluble 17-DMAG is equally effective as 17-AAG. HSP27, besides HSP70, may represent an effective response marker of successful HSP90 inhibition.

AB - Chemotherapy (CT) options in pancreatic cancer (PC) are limited to gemcitabine and 5-fluorouracil (5-FU). Several identified molecular targets in PC represent client proteins of HSP90. HSP90 is a promising target since it interferes with many oncogenic signaling pathways simultaneously. The aim of this study was to evaluate the efficacy of different HSP90 inhibitors in gemcitabine and 5-FU resistant PC. PC cell lines 5061, 5072 and 5156 were isolated and brought in to culture from patients being operated at our institution. L3.6pl cell line served as a control. Anti-proliferative efficacy of three different HSP90 inhibitors (17-AAG, 17-DMAG and 17-AEPGA) was evaluated by the MTT assay. Alterations in signaling pathway effectors and apoptosis upon HSP90 inhibition were determined by western blot analysis and annexin V/PI staining. The cell lines 5061, 5072 and 5156 were resistant to gemcitabine and 5-FU. In contrast 17-AAG and the water-soluble derivates 17-DMAG and 17-AEPGA displayed high anti-proliferative activity in all tested cell lines. The calculated IC50 was below 1 µM. Highly significant down regulation of epidermal-growth-factor-receptor, insulin-like-growth-factor-receptor-1, AKT and MAPK reflected the intracellular molecular signaling-network disruption. Furthermore, besides HSP70 also HSP27 was upregulated in all cell lines. Apoptosis occurred early under HSP90 inhibition and was determined by annexin V/PI staining and CASPASE-3 and PARP assay. In contrast, gemcitabine treated cells did not show any apoptosis. HSP90 inhibition disrupts multiple signaling cascades in gemcitabine and 5-FU resistant PC simultaneously and promotes cancer cell apoptosis. Watersoluble 17-DMAG is equally effective as 17-AAG. HSP27, besides HSP70, may represent an effective response marker of successful HSP90 inhibition.

U2 - 10.1007/s10495-016-1332-4

DO - 10.1007/s10495-016-1332-4

M3 - SCORING: Journal article

C2 - 27878398

VL - 22

SP - 369

EP - 380

JO - APOPTOSIS

JF - APOPTOSIS

SN - 1360-8185

IS - 3

ER -