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Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
Gemcitabine inhibits viability, growth, and metastasis of osteosarcoma cell lines
Takashi Ando1, Jiro Ichikawa, Atsushi Okamoto
1Department of Orthopaedic Surgery, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Tamaho, Yamanashi 409-3898, Japan. takakun@yin.or.jp
Abstract:
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.
Insights
Gemcitabine demonstrates significant anti-tumor activity against osteosarcoma cell lines in vitro and in vivo. This cytosine arabinoside analog effectively reduced tumor size and metastasis, suggesting potential therapeutic applications for osteosarcoma patients.
Area of Science:
- Oncology
- Pharmacology
Background:
- Osteosarcoma remains a challenging cancer with limited effective treatments.
- Gemcitabine, a cytosine arabinoside analog, shows anti-tumor activity in various cancers, but its efficacy in osteosarcoma requires further investigation.
Purpose of the Study:
- To evaluate the anti-tumor activity of gemcitabine in human osteosarcoma cell lines and in a murine model.
Main Methods:
- In vitro cytotoxicity assays were performed on nine human osteosarcoma cell lines treated with gemcitabine.
- DNA synthesis inhibition and apoptosis induction were assessed in HOS and MG63 cell lines.
- In vivo studies involved treating C3H mice bearing murine osteosarcoma (LM8) with gemcitabine.
Main Results:
- Gemcitabine exhibited significant cytotoxicity (>100 nM) against all tested osteosarcoma cell lines.
- Inhibition of DNA synthesis and induction of apoptosis were observed in HOS and MG63 cells.
- In vivo, gemcitabine treatment reduced primary tumor size, increased apoptosis, and virtually eliminated lung metastasis in mice.
Conclusions:
- Gemcitabine possesses potent anti-tumor activity against osteosarcoma, both in vitro and in vivo.
- These findings support the potential clinical application of gemcitabine for treating osteosarcoma.
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