Eradication of osteosarcoma lung metastasis using intranasal gemcitabine

Anti-cancer Drugs
Shu-Fang JiaEugenie S Kleinerman

Abstract

We sought to determine whether gemcitabine, a new pyrimidine antimetabolite, could inhibit the growth of human osteosarcoma cells (OS) in vitro and in vivo. Four human OS cell lines (MG-63, TE-85, SAOS-2 and SAOS-LM7) were used to assess the activity of the drug in vitro. Gemcitabine caused growth inhibition and cell death in all four cell lines as measured using the MTT and colony-forming assays (IC(50) = 6.5 nM-9 microM and 7-14 nM, respectively). Using our newly developed human SAOS-LM7 OS lung metastasis mouse model, we assessed the in vivo activity of gemcitabine given i.p. and intranasally (i.n.). Mice were treated twice weekly for 3 weeks and then once weekly for 3 weeks using either i.p. or i.n. gemcitabine starting 4 weeks after tumor cell injection. The i.p. injection, at 120 mg/kg, resulted in a decrease in lung weights and the size of the nodules. However, no significant reduction in the number of metastatic nodules was seen (control median: >200 versus gemcitabine median: 150, p = 0.084). In contrast, the number of lung metastases was significantly decreased in mice that received i.n. gemcitabine at 15 (median: 1; range: 0-115, p<0.005) and 12 mg/kg (median: 41; range: 7-163, p = 0.005) when compared with control m...Continue Reading

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Citations

Oct 13, 2006·Journal of Cancer Research and Clinical Oncology·Crispin R DassPeter F M Choong
Jan 1, 2009·Expert Opinion on Medical Diagnostics·Colin Kong, Marc F Hansen
Jan 30, 2015·Journal of the American Chemical Society·Fuwu ZhangKaren L Wooley
Mar 7, 2017·PloS One·Jonathan GillDavid S Geller
Apr 1, 2005·International Journal of Cancer. Journal International Du Cancer·Nadezhda V Koshkina, Eugenie S Kleinerman
Apr 27, 2010·Advances in Anatomic Pathology·José Luis OrdóñezEnrique de Alava
Aug 26, 2010·Expert Review of Anticancer Therapy·Timothy M Fan
Oct 21, 2004·Anti-cancer Drugs·Corinne AlcouffeXavier Ronot

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