Gemcitabine inhibits viability, growth, and metastasis of osteosarcoma cell lines.
Gemcitabine (dFdCyd) is an analog of cytosine arabinoside with anti-tumor activity in several human cancers. However, the efficacy of this compound in osteosarcoma has not been fully elucidated. Here we assessed the anti-tumor activity of gemcitabine using osteosarcome cell lines. In 9 human osteosarcoma cell lines (G292, HOS, MG63, NY, SaOS, HuO, HuO-3N1, HuO9, HuO9-N2), gemcitabine at the doses of >100 nM showed significant cytotoxicity. In HOS and MG63 cell lines, gemcitabine inhibited DNA synthesis as determined by IdU labeling assay and induced apoptosis as determined by DNA fragmentation assay and May-Giemsa staining. In C3H mice inoculated s.c. with a murine osteosarcoma cell line, LM8, treatment of the mice with gemcitabine showed reduced size of the primary tumor associated with increased apoptotic cells and a virtual absence of metastatic lesions in the lung. Gemcitabine thus had anti-tumor activity on osteosarcoma cell lines both in vitro and in vivo. The result would provide a cellular basis for application of gemcitabine to patients with osteosarcoma.
Ando
Takashi
T
Department of Orthopaedic Surgery, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Tamaho, Yamanashi 409-3898, Japan. takakun@yin.or.jp
Ichikawa
Jiro
J
Okamoto
Atsushi
A
Tasaka
Kachio
K
Nakao
Atsuhito
A
Hamada
Yoshiki
Y
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D012516:Osteosarcoma / Q000188:drug therapy* / Q000556:secondary; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D004247:DNA; D000093542:Gemcitabine