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M.–A. Economou, C. All–Ericsson, S. Seregard, L. Girnita, O. Larsson; The Novel Agent PPP Is More Effective Than Traditional Chemotherapeutic Drugs in Causing Uveal Melanoma Cell Death in vitro . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2228.
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© ARVO (1962-2015); The Authors (2016-present)
We have previously shown that the cyclolignan picropodophyllin (PPP) efficiently blocks the insulin–like growth facotor–1 receptor (IGF–1R) and causes cell death in uveal melanoma cell lines. Further, PPP induces significant tumor regression in animal models. In this study we compared the effectiveness of PPP with imatinab mesylate (Gleevec) and more traditional antineoplastic agents such as 5–fluorouracil (5–FU), doxorubicin and cisplatin and investigated the potential synergistic effects of these drugs.
Four different uveal melanoma cell lines (OCM–1, OCM–3, OCM–8, 92–1) were treated with different concentrations of PPP alone and in combination with Gleevec, 5–FU, doxorubicin and cisplatin for 48 hrs. Cell survival was assessed by XTT. Cell viability determinations were performed using the Cell proliferation kit II.
The IC50 of PPP for the four different ocular melanoma cell lines were between 0.015–0.035 µM, for Gleevec 0.18–0.25 µM, for 5–FU 3–5mM, for Doxorubicin 8–10 µM and for Cisplatin 1–6 µM. A concentration of 0.04 µM PPP reduced cell survival by 60–90%. Generally, the OCM–8 cell line was generally more sensitive for exposure of PPP, Cisplatine and Imitanib. There was no synergistic effect for any combination of these drugs in any of the cell lines
PPP alone efficiently decreased viability of the 4 uveal melanoma cell lines studied.
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