Survivin inhibitor YM155 suppresses gastric cancer xenograft growth in mice without affecting normal tissues

Oncotarget
Xiao Jiao ChengShui Ping Tu

Abstract

Survivin overexpression is associated with poor prognosis of human gastric cancer, and is a target for gastric cancer therapy. YM155 is originally identified as a specific inhibitor of survivin. In this study, we investigated the antitumor effect of YM155 on human gastric cancer. Our results showed that YM155 treatment significantly inhibited cell proliferation, reduced colony formation and induced apoptosis of gastric cancer cells in a dose-dependent manner. Accordingly, YM155 treatment significantly decreased survivin expression without affecting XIAP expression and increased the cleavage of apoptosis-associated proteins caspase 3, 7, 8, 9. YM155 significantly inhibited sphere formation of gastric cancer cells, suppressed expansion and growth of the formed spheres (cancer stem cell-like cells, CSCs) and downregulated the protein levels of β-catenin, c-Myc, Cyclin D1 and CD44 in gastric cancer cells. YM155 infusion at 5 mg/kg/day for 7 days markedly inhibited growth of gastric cancer xenograft in a nude mouse model. Immunohistochemistry staining and Western Blot showed that YM155 treatment inhibited expression of survivin and CD44, induced apoptosis and reduced CD44+ CSCs in xenograft tumor tissues in vivo. No obvious patholog...Continue Reading

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Citations

Jun 28, 2017·Translational Oncology·Marieke A de GraaffJudith V M G Bovée
Apr 8, 2021·Cellular and Molecular Life Sciences : CMLS·Olga Sokolova, Michael Naumann

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Methods Mentioned

BETA
xenograft
FACS
antisense oligonucleotide
flow cytometry

Software Mentioned

Primer Quest SM

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