Introduction

Despite advances in the understanding of cancers across species, the treatment paradigm for both human and canine osteosarcoma (OS) has not changed in decades. SHIP proteins, important phosphatases in the PI3K cell signaling tree, have been shown to promote cell survival in various neoplasms, but their role in canine OS has not been evaluated. Therefore, we sought to determine the in vitro biologic effects of several novel SHIP inhibitors.

Methods

MTS experiments assessed cell viability in three established canine OS lines (Abrams, D-17, and HMPOS). Cells were treated with 3-AC, K118, K149, and K161 at concentrations ranging from 1.25–10.0 µM. To assess cell migration, confluent canine OS cells were wounded using BioTek’s Autoscratch Tool followed by treatment with K118. Wells were imaged for 72 hours post-treatment using the Lionheart FX.

Results

MTS data demonstrated that SHIP inhibitors exhibit a time and concentration dependent decrease in cell viability. The greatest effect for all inhibitors occurred 72 hours post-treatment. K118 was chosen for further evaluation as it demonstrated the highest potency of SHIP inhibitors tested. K118 inhibited wound healing and cell migration; its greatest effects were noted at 1.25 µM and 2.5 µM concentrations.

Conclusion

Further studies of SHIP inhibitors should investigate the mechanism of cell signaling pathway interference, specifically in the PI3K/mTOR pathway. Clarifying the role of SHIP proteins in OS pathogenesis could promote further in vivo studies, assessing biologic efficacy.

Funding Information

This work was funded by extramural (Morris Animal Foundation Veterinary Scholar Program) and intramural (Phi Zeta Research Grant Proposal - University of Missouri College of Veterinary Medicine) grants. Ms. Allen received a funded Boehringer-Ingelheim Veterinary Student Research Award for this work.