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Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro
Published on: March 18, 2014
YM155 enhances the cytotoxic activity of etoposide against canine osteosarcoma cells
Siew Mei Ong1, Kohei Saeki1, Mun Keong Kok2
1Laboratory of Veterinary Surgery, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Abstract:
Canine osteosarcoma (OSA) is an aggressive and highly malignant primary bone tumor. Its poor survival outcome remains problematic despite recent advances in anti-cancer therapy, therefore highlighting the need for alternative treatment options or drug repositioning. The aim of this study was to determine if YM155, a small-molecule survivin inhibitor, potentiates the chemotherapeutic efficacy of etoposide against canine OSA in vitro and in vivo. In cell culture, YM155 enhanced the cytotoxic effect of etoposide against canine OSA cell lines; however, the molecular mechanism behind this effect was heterogeneous, as only one cell line had an elevated apoptotic level. In addition, this effect was not associated with survivin suppression in two of the cell lines. These results suggest that the molecular target of YM155 is not restricted to survivin alone. When tested on a murine xenograft model, the average tumor volume of the combination treatment group (YM155, 5 mg/kg, intraperitoneally, 5 consecutive days/week; and etoposide, 20 mg/kg, intraperitoneally, every 5 days) was 66% smaller than the control group, although this difference was not statistically significant (P=0.17). Further studies to improve the treatment protocol are necessary to confirm the findings of this study.
Insights
YM155 combined with etoposide showed potential against canine osteosarcoma (OSA) in vitro and in vivo. While not statistically significant in vivo, the combination warrants further investigation for treating this aggressive bone cancer.
Area of Science:
- Veterinary Oncology
- Pharmacology
- Cancer Biology
Background:
- Canine osteosarcoma (OSA) is a highly malignant bone tumor with poor prognosis.
- Current anti-cancer therapies offer limited survival benefits, necessitating novel treatment strategies.
- Drug repositioning of existing agents like YM155 presents a viable avenue for alternative therapies.
Purpose of the Study:
- To evaluate the potentiating effect of YM155, a survivin inhibitor, on etoposide's efficacy against canine OSA.
- To investigate the in vitro and in vivo therapeutic potential of this drug combination.
Main Methods:
- Canine OSA cell lines were treated with YM155 and etoposide to assess cytotoxicity and apoptosis.
- A murine xenograft model of canine OSA was used to evaluate the combination therapy's in vivo efficacy.
- Tumor volume and statistical significance were measured for the combination treatment versus control.
Main Results:
- YM155 enhanced etoposide's cytotoxic effect on canine OSA cell lines in vitro.
- The molecular mechanism of YM155's action was heterogeneous and not solely dependent on survivin suppression.
- Combination therapy reduced tumor volume by 66% in a murine model, though not reaching statistical significance (P=0.17).
Conclusions:
- YM155 may have therapeutic potential beyond survivin inhibition in canine OSA.
- The combination of YM155 and etoposide warrants further investigation with optimized protocols.
- Additional research is needed to confirm the efficacy and refine treatment strategies for canine osteosarcoma.
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