Effects of trastuzumab emtansine on canine osteosarcoma cells.

Abstract

Human epidermal growth factor receptor 2 (HER2) is a known therapeutic target in canine osteosarcoma (OSA); however, the efficacy of anti-HER2 antibody drugs remains unclear. This study aimed to investigate the effects of the anti-HER2 antibody drugs including trastuzumab and trastuzumab emtansine (T-DM1) on canine OSA cell lines in vitro and in vivo. Four canine OSA cell lines (HMPOS, POS, OOS, and HOS) were used. Western blotting revealed HER2 protein expression in all the cell lines. Although water-soluble tetrazolium salt assays showed growth inhibitory activity of trastuzumab and T-DM1 against all the cell lines in vitro, the activity of T-DM1 was significantly stronger than that of trastuzumab. Flow cytometric analysis of the canine OSA cell line (HMPOS) revealed that T-DM1, but not trastuzumab, significantly increased the sub-G1 phase fraction in cell cycle analyses and the percentage of early and late apoptotic cells in annexin V apoptotic assays. For in vivo experiments, canine OSA cells (HMPOS) were subcutaneously injected into nude mice. Six days after inoculation, trastuzumab, T-DM1, or the vehicle control was administered intraperitoneally once per week. Survival until the tumor volume in the canine OSA-engrafted mice reached mean final tumor volume in the T-DM1 group was significantly longer in the T-DM1 group, but not in the trastuzumab group, compared to the vehicle control group. These findings indicated that T-DM1 exerts antitumor effects on canine OSA cells in vitro and in vivo, possibly by inducing apoptosis due to DM1.