Oncology

Research Abstract

O08 - YM155 Inhibits the Growth of Canine Squamous Cell Carcinoma Cells with High Expression of Survivin

Thursday, June 14
3:15 PM - 3:30 PM
Location: WSCC 615

Survivin is highly expressed in various malignancies and functions as an inhibitor of apoptosis. YM155, an imidazolium-based small molecule, has potent inhibitory activity to survivin; therefore, it is considered a potential new class of anti-tumor agents. In the current study, we screened for various canine tumor cell lines that have susceptibility to YM155. On the basis of the screening, we focused on squamous cell carcinoma (SCC) and growth inhibitory mechanisms of YM155 in SCC cells were investigated.


Among ten cell lines (eight tumor types) screened, only SCC cell line showed substantial susceptibility to YM155. Based on this finding, seven canine SCC cell lines were examined for susceptibility to the cytotoxic effects of YM155. YM155 clearly inhibited the growth of two cell lines HAPPY and SQ4. These cell lines, but not other cell lines, highly expressed survivin. In HAPPY cells, YM155 inhibited expression of survivin at the both mRNA and protein level. In contrast, YM155 down-regulated survivin expression only at the protein level in SQ4 cells. Moreover, YM155 suppressed cell growth mostly by induction of apoptosis in HAPPY cells but not in SQ4 cells. 


Our results suggested that canine SCCs with high cellular expression of survivin are susceptible to survivin inhibitor YM155. There are different mechanisms in YM155-induced suppression of survivin expression, namely at the transcriptional and post-transcriptional levels. Moreover, YM155 was found to induce growth inhibition of SCC cells by induction of not only apoptotic cell death, but also non-apoptotic cell death.

Ryo Miyamoto, DVM

Graduate student
Nippon veterinary and life science university

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