p38 MAP kinase inhibition promotes primary tumour growth via VEGF independent mechanism.

World Journal of Surgical Oncology
Adrian W O'SullivanHenry P Redmond

Abstract

The surgical insult induces an inflammatory response that activates P38 MAP kinases and solid tumours can also release cytokines. Therfore inhibition of these pathways may reduce tumour growth We set out to examine the effects of P38-MAPK inhibition on apoptosis, proliferation, VEGF release and cell cycle effects in-vitro and on primary tumour growth in-vivo. 4T-1 cells (2 x 105 cells/well) were incubated, in 24 well plates with control, 25, 50 or 100 ng/ml of SB-202190 for 24 hours. Cells were subsequently asessed for apoptosis, proliferation, VEGF release and cell cycle analysis. Balb-c mice each received 1 x 106 4T 1 cells subcutaneously in the flank and were then randomised to receive control or SB202190 (2.5 microM/kg) by intraperitoneal injection daily. Tumour size was measured alternate days and at day 24 animals were sacrificed and serum VEGF assessed. P38-MAPK inhibition in-vitro resulted in a significant reduction in proliferation (75.2 +/- 8.4% vs. 100 +/- 4.3%, p < 0.05) and G1 cell cycle phase(35.9 +/- 1.1% vs. 32.5 +/- 0.6%, p < 0.05) but no significant changes in apoptosis or VEGF levels. In-vivo, P38-MAPK inhibition resulted in an increase in primary tumour growth (155.6 +/- 34.9 vs. 86.7 +/- 18.2 mm3, p < 0.05)...Continue Reading

References

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Jan 23, 2008·The Journal of Sexual Medicine·Hussein GhanemRany Shamloul
Aug 5, 2008·The Journal of Surgical Research·Adrian W O'SullivanHenry P Redmond

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Citations

Aug 23, 2011·PloS One·Sumedha W KarmarkarShelley A Tischkau
Jan 15, 2014·Oncogene·A Avivar-ValderasJ A Aguirre-Ghiso
Nov 6, 2013·Journal of Molecular Neuroscience : MN·Daniel Ortuño-SahagúnC Beas Zárate
Jul 21, 2016·American Journal of Respiratory Cell and Molecular Biology·Heather L MendenVenkatesh Sampath

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BETA
ELISA

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CellQuest

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