Microsoft powerpoint - posteraacr042008ml.ppt

Antitumor activity of PBI-1737 in xenograft human prostate
(PC-3) cancer by inhibition of cell adhesion and migration
Mouna Lagraoui, Brigitte Grouix, Marie-Ève Fafard, Dannyck Gaudreau, Natalie St-Amant, Lilianne Geerts,
François Sarra-Bournet, Valérie Perron, Jean-Simon Duceppe, Boulos Zacharie, Christopher Penney and Lyne Gagnon ProMetic BioSciences Inc., Laval, Québec, Canada H7V 5B7 ABSTRACT
METHODS AND RESULTS
Cell adhesion, proteolytic degradation In Vitro Studies
In vitro cell-matrix adhesion was In Vivo Studies
of extracellular matrix and cell migration determined by fluorescence. Adherence of The xenogenic human prostate tumor PC-3 cells were obtained from ATCC (CRL1435). calcein-AM labeled PC-3 cells to laminin, Cells were grown in RPMI-1640 containing 10% fetal bovine serum. At day 0, 50 μl of viable PC-3 (1.5 to 2X106) cells were injected intradermally to produce localized tumors in 6- to 8-week old male CD1 nu/nu mice (Charles River). Animals were monitored by Effect of PBI-1737 on PC-3 cell adhesion
manual palpation for evidence of tumor. When the tumors reached a satisfactory volume, to laminin
mice were randomized and then treated with vehicle (saline), cyclophosphamide (Cytoxan; positive control, 100 mg/kg, iv once a week) or PBI-1737 (per os, 50 mg/kg, daily). Mice Figures 5 and 6 represent the antitumor efficacy of PBI-1737 with or without
cyclophosphamide on the xenograft human prostate PC-3 tumor. Oral administration of PBI-1737 induces a significant (p < 0.05) inhibition of tumor volume with a T/C between 14% to 40%. Cyclophosphamide induces a significant inhibition (p < 0.05) of tumor 5.0 10.0 20.0 40.0 60.0 80.0
volume with a T/C between 1% to 39%. Mice treated with the combination of PBI-1737 Concentration (μM)
cyclophosphamide and PBI-1737 demonstrated a significant (p < 0.01) inhibition of tumor volume with a T/C between 1% to 40% followed by tumor regression after day 43.
Effect of PBI-1737 on PC-3 cell adhesion
Effect of PBI-1737, cyclophosphamide (CY) and
Antitumor efficacy of PBI-1737, cyclophosphamide
Effect of PBI-1737 on EGF-induced
to matrigel
combination of PBI-1737 + CY on xenograft
(CY) and combination of PBI-1737 + CY on xenograft
PC-3 cell migration or invasion
human prostate PC-3 tumor growth
human prostate PC-3 tumor
Cyclophosphamide (CY)
Cyclophosphamide (CY)
PBI-1737
PBI-1737
PBI-1737 + CY
PBI-1737 + CY
mg/kg) induces a significant (p < 0.05) Injection of CY
EGF + PBI-1737
5.0 10.0 20.0 40.0 60.0 80.0
PBI-1737 Concentration (μM)
inhibition (p < 0.05) of tumor volume Effect of PBI-1737 on PC-3 cell adhesion
to collagen
PBI-1737
PBI-1737
PBI-1737
significant (p < 0.01) inhibition of tumor RFU 15000
Figure 1 represents the effect of
These in vivo and in vitro data indicate 5.0 10.0 20.0 40.0 60.0 80.0
that oral administration of PBI-1737 migration of PC-3 cells treated PBI-1737 Concentration (μM)
CONCLUSION
demonstrated significant antitumor with mitomycin compared to activity via an inhibition of cell adhesion ƒPBI-1737 is a novel, low molecular ƒPBI-1737 displays significant antitumor Figures 2, 3 and 4 represent the effect of
activity against human prostate cancer. A cancer cells. A synergistic effect concentrations of PBI-1737 to the PBI-1737 on PC-3 cell adhesion to laminin, ƒ regression of the tumor is also observed cell culture induces an inhibition of matrigel and collagen, respectively. The addition of increasing concentrations of PBI-1737 inhibits in a dose dependent
manner PC-3 cell adhesion to laminin, Taken together, these data suggest a promising role of PBI-1737 in the control of
matrigel and collagen.
prostate tumor progression.

Source: http://www.prometic.com/docs/misc/posteraacr042008ml.pdf