ENMD-1198, a novel tubulin-binding agent reduces HIF-1alpha and STAT3 activity in human hepatocellular carcinoma(HCC) cells, and inhibits growth and vascularization -4

Y) or diluent when tumors became palpable. A) Treatment with ENMD-1198 led to a significant growth inhibition of xenografted hepatocellular tumors, compared to controls (*P < 0.05). B) Final tumor weights (day 19) in the ENMD-1198 treatment group were significantly lower, compared to excised tumors of the control group (*P < 0.05). Bars: mean ± SEM.<p><b>Copyright information:</b></p><p>Taken from "ENMD-1198, a novel tubulin-binding agent reduces HIF-1alpha and STAT3 activity in human hepatocellular carcinoma(HCC) cells, and inhibits growth and vascularization "</p><p>http://www.biomedcentral.com/1471-2407/8/206</p><p>BMC Cancer 2008;8():206-206.</p><p>Published online 23 Jul 2008</p><p>PMCID:PMC2496914.</p><p></p

ENMD-1198, a novel tubulin-binding agent reduces HIF-1alpha and STAT3 activity in human hepatocellular carcinoma(HCC) cells, and inhibits growth and vascularization -5

Howed that vessel area was significantly reduced in ENMD-1198-treated tumors (*P < 0.01). B) ENMD-1198 significantly decreased the number of proliferating (BrdUrd-positive) tumor cells in tissue sections (*P < 0.01). For both vessel area and cell proliferation, representative images are illustrated. Results shown are the mean ± SEM. C) Western blot analysis for HIF-1α expression in HCC tumors showed a substantial reduction of HIF-1α in ENMD-1198 treated tumors.<p><b>Copyright information:</b></p><p>Taken from "ENMD-1198, a novel tubulin-binding agent reduces HIF-1alpha and STAT3 activity in human hepatocellular carcinoma(HCC) cells, and inhibits growth and vascularization "</p><p>http://www.biomedcentral.com/1471-2407/8/206</p><p>BMC Cancer 2008;8():206-206.</p><p>Published online 23 Jul 2008</p><p>PMCID:PMC2496914.</p><p></p

ENMD-1198, a novel tubulin-binding agent reduces HIF-1alpha and STAT3 activity in human hepatocellular carcinoma(HCC) cells, and inhibits growth and vascularization -2

Educed cancer cell motility and blunted the response to either EGF, or HGF (*P < 0.01). B) The effects on cancer cell invasiveness were evaluated using Matrigel-coated inserts. ENMD-1198 (2.5 μM) significantly abrogated EGF- and HGF-mediated invasive properties of hepatocellular carcinoma cells, compared to controls (*P < 0.01 for all). Experiments were performed in triplicates and results were confirmed in a second cell line (HepG2). Bars: SEM.<p><b>Copyright information:</b></p><p>Taken from "ENMD-1198, a novel tubulin-binding agent reduces HIF-1alpha and STAT3 activity in human hepatocellular carcinoma(HCC) cells, and inhibits growth and vascularization "</p><p>http://www.biomedcentral.com/1471-2407/8/206</p><p>BMC Cancer 2008;8():206-206.</p><p>Published online 23 Jul 2008</p><p>PMCID:PMC2496914.</p><p></p

ENMD-1198, a novel tubulin-binding agent reduces HIF-1alpha and STAT3 activity in human hepatocellular carcinoma(HCC) cells, and inhibits growth and vascularization -1

R pre-incubation with ENMD-1198 (16 hours). A) HUH-7 cells and B) HepG2 cells were used for experiments. ENMD-1198 abrogated EGF-induced phosphorylation of Akt (HUH-7), FAK (HUH-7), p44/42 MAPK (HepG2), and STAT3 (HUH-7, HepG2). β-actin served as a loading control.<p><b>Copyright information:</b></p><p>Taken from "ENMD-1198, a novel tubulin-binding agent reduces HIF-1alpha and STAT3 activity in human hepatocellular carcinoma(HCC) cells, and inhibits growth and vascularization "</p><p>http://www.biomedcentral.com/1471-2407/8/206</p><p>BMC Cancer 2008;8():206-206.</p><p>Published online 23 Jul 2008</p><p>PMCID:PMC2496914.</p><p></p

ENMD-1198, a novel tubulin-binding agent reduces HIF-1alpha and STAT3 activity in human hepatocellular carcinoma(HCC) cells, and inhibits growth and vascularization -3

Western blot analysis of whole protein showed that ENMD-1198 effectively blunted hypoxic induction of HIF-1α protein. B) In addition, treatment with ENMD-1198 down-regulated constitutive VEGF-A mRNA levels in HCC cells (HepG2), as measured by real-time PCR (* P < 0.01) (n = 3/group). VEGF-A mRNA expression is normalized to β-actin. C) ELISA analysis for VEGF in culture supernatants (HepG2). Hypoxia (20 h, 1% O) markedly increased VEGF protein. ENMD-1198 treatment lowered VEGF secretion under hypoxic conditions (*P < 0.05). D) Western blot analysis for VEGF. Cells were incubated under either non-hypoxic, or hypoxic conditions ± ENMD-1198. Treatment with ENMD-1198 slightly lowered the hypoxic induction of VEGF, as determined by densitometry. Bars: SEM.<p><b>Copyright information:</b></p><p>Taken from "ENMD-1198, a novel tubulin-binding agent reduces HIF-1alpha and STAT3 activity in human hepatocellular carcinoma(HCC) cells, and inhibits growth and vascularization "</p><p>http://www.biomedcentral.com/1471-2407/8/206</p><p>BMC Cancer 2008;8():206-206.</p><p>Published online 23 Jul 2008</p><p>PMCID:PMC2496914.</p><p></p

ENMD-1198, a novel tubulin-binding agent reduces HIF-1alpha and STAT3 activity in human hepatocellular carcinoma(HCC) cells, and inhibits growth and vascularization -0

antiproliferative effects on HCC cells with an ICat 2.5 μM in both cell lines (data shown for HUH-7) (*P < 0.05). Bars represent mean ± SEM from three independent experiments. Bars: SEM.<p><b>Copyright information:</b></p><p>Taken from "ENMD-1198, a novel tubulin-binding agent reduces HIF-1alpha and STAT3 activity in human hepatocellular carcinoma(HCC) cells, and inhibits growth and vascularization "</p><p>http://www.biomedcentral.com/1471-2407/8/206</p><p>BMC Cancer 2008;8():206-206.</p><p>Published online 23 Jul 2008</p><p>PMCID:PMC2496914.</p><p></p